Pyrimidine derivatives

ABSTRACT

The present invention relates to trisubstituted pyrimidines of formula (I)  
                 
 
     wherein  
     0R a  to R e  are defined as in claim 1, which are suitable for the treatment of illnesses characterised by excessive or abnormal cell proliferation, the use thereof for preparing a pharmaceutical composition with the abovementioned properties, and processes for the preparation thereof.

RELATED APPLICATIONS

[0001] Benefit of U.S. Provisional Application Serial No. 60/330,145,filed on Oct. 17, 2001 is hereby claimed, and said application is hereinincorporated by reference in its entirety.

FIELD OF THE INVENTION

[0002] The invention relates to 2,4,5-trisubstituted pyrimidines offormula (I)

[0003] wherein the groups R_(a) to R_(e) have the meanings given in theclaims and in the specification, processes for preparing them and theuse thereof as pharmaceutical compositions, particularly aspharmaceutical compositions for the treatment of illnesses characterisedby excessive or abnormal cell proliferation.

BACKGROUND OF THE INVENTION

[0004] International Patent Application WO 00/53595 describes the use of2,4,5-substituted pyrimidines, with a heterocyclic group in the 4position and an anilino group in the 2 position, which in turn carries aside chain with the length of at least one n-propyl group, as an activecomponent with an anticancer activity.

[0005] Moreover, International Patent Application WO 00/39101 proposesthe use of 2,4,5-substituted pyrimidines as compounds with an anticanceractivity, which are linked in the 2 and 4 positions to an aromatic orheteroaromatic ring, at least one of which has a side chain with thelength of at least one n-propyl group.

[0006] Antiviral 2,4,5-substituted pyrimidines, wherein the groups R_(c)and R_(d) at the nitrogen of the 4 position form a heteroaromaticfive-membered ring, are known from International Patent Application WO99/41253.

[0007] International Patent Application WO 97/19065 also proposes theuse of 2,4,5-substituted pyrimidines, with a 3,4-dialkoxy-anilino groupin the 2 position, as kinase inhibitors.

[0008] For 2,4,5-substituted pyrimidines which carry (hetero)aryls inthe 2 and 4 positions (WO00/27825), as well as for 2,4,5-substitutedpyrimidines which carry a (hetero)aryl group functionalised with anitrile group in position 2 or 4 (EPO 945 443), an antiviral activityhas been described.

[0009] The aim of the present invention is to find new active substanceswhich can be used for the prevention and/or treatment of diseasescharacterised by excessive or abnormal cell proliferation.

DETAILED DESCRIPTION OF THE INVENTION

[0010] Surprisingly, it has now been found that the compounds of generalformula (I)

[0011] have valuable pharmacological properties, particularly aninhibiting activity on protein kinases such as SRC kinases, PLK kinaseand particularly cyclin-dependent kinases (CDKs, such as e.g. CDK1,CDK2, CDK3, CDK4, CDK5, CDK6, CDK7, CDK8 and CDK9 with their specificcyclins A, B1, B2, C, D1 D2, D3, E, F, G1, G2, H, I, K and viral cyclin)as well as on the kinase activity of Aurora B. The compounds exhibitvaluable pharmacological properties, such as neuroprotection and aninhibiting activity on the proliferation of cultivated human tumourcells.

[0012] In view of their biological properties the new compounds ofgeneral formula I, their isomers and their physiologically acceptablesalts are suitable for treating diseases characterised by excessive orabnormal cell proliferation.

[0013] Such diseases include (with no claim to completeness): viralinfections (e.g. HIV and Kaposi's sarcoma); infections caused by adeno,influenza or cytomegaly viruses); bacterial, fungal and/or parasiticinfections; skin diseases (e.g. psoriasis, eczema, keratoses); bonediseases; cardiovascular diseases (e.g. restenosis and hypertrophism).They may also be useful in protecting proliferating cells (e.g. hair,intestinal, blood and progenitor cells) against DNA damage caused byradiation, UV treatment and/or cytostatic treatment (Davis et al., 2001,Science, 291, 134-137).

[0014] In addition, the compounds are useful for immunosuppression (e.g.in organ transplantation) and for the prevention or treatment ofinflammation and autoimmune diseases (e.g. colitis, arthritis,Alzheimer's disease, glomerulonephritis and wound healing).

[0015] In particular, these compounds are useful as cytotoxic orcytostatic active substances for the treatment or prevention of diseasesbased on the proliferation of tumour cells.

[0016] The tem “cytotoxic compound” denotes a chemical which has a toxiceffect on living cells, particularly an active substance which destroyscancer cells. The term “cytostatic compound” denotes a compound whichsuppresses cell growth and division and thus also suppresses cellproliferation.

[0017] Accordingly, in another aspect, the invention relates to the useof a compound of the invention for preparing a pharmaceuticalcomposition for the treatment of cancer. The invention further relatesto a method for treating cancer by administering an effective amount ofa pharmaceutical composition according to the invention to the patient.The indications include the treatment of cancer, in particular:

[0018] 1) The treatment of malignant neoplasias and carcinomas includingbreast cancer, neoplasias of the digestive tract (colorectal carcinoma,anal carcinoma, pancreatic carcinoma, gastric carcinoma, oesophagealcarcinoma, hepatocellular carcinoma, gall bladder carcinoma), lungcancer, tumours of the head and neck, ovarian tumours, tumours of theadnexa, endometrial carcinoma, prostate carcinoma, testicular tumours,urothelial carcinoma, kidney cell carcinoma, skin tumours, thyroidcarcinoma and endocrinically active tumours.

[0019] 2) Sarcomas of the bones and soft tissues: osteosarcoma, softtissue sarcoma, Ewing's sarcoma, chondrosarcoma, fibrosarcoma, malignantfibrous histiocytoma (NFH), leiomyosarcomas and other soft tissuesarcomas;

[0020] 3) Malignant tumours of haemopoiesis: Hodgkin's and non-Hodgkin'slymphomas; leukaemias, multiple myeloma, myeloproliferative andmyelodysplastic syndromes;

[0021] 4) Neuroectodermal tumours: peripheral nerve sheath tumours,medulloblastomas; neuroblastomas, retinoblastomas, astrocytomas andother brain tumours;

[0022] 5) Melanomas;

[0023] 6) Mesotheliomas.

[0024] The new compounds of formula I may also be used for theshort-term or long-term treatment of the abovementioned diseases,optionally in combination with other “state-of-the-art” compounds suchas other cytostatics, antibodies, targeted therapies such as inhibitorsof the EGF, Her2 or VEGF signal transduction pathway or angiogenesisinhibitors. The CDK1 inhibitor olomoucine was found to have asynergistic effect with cytotoxic substances in cell culture (Ongkeko etal., 1995, J. Cell Sci., 108, 2897). The compounds mentioned may beadministered before or after the administration of known antitumourdrugs or cytotoxic substances. It is known that the cytotoxic activityof the CDK inhibitor flavopiridol in conjunction with cancer drugs isinfluenced by the sequence in which they are administered. (CancerResearch, 1997, 57, 3375).

[0025] Examples of cytostatics which are suitable for use in conjunctionwith the compounds of formula I are anthracyclins such as doxorubicin,analogues of methotrexate such as methotrexate, pritrexime, trimetrexateor DDMP, melphalan, analogues of cisplatin such as cisplatin, J216,JM335, bis(platinum), oxaliplatin or carboplatin, analogues of purinesand pyrimidines such as cytarabine, gemcitabine, azacitidine,6-thioguanine, fludarabine or 2-deoxycoformycin and analogues of otherchemotherapeutic agents such as 9-amino-camptothecin,D,L-aminoglutethimide, trimethoprim, pyrimethamine, mitomycin C,mitoxantrone, cyclophosphamide, 5-fluorouracil, capecitabine,estramustine, podophyllotoxin, bleomycin, epothilone A, B, C or D andderivatives of epothilone as described for example in U.S. Pat. No.6,204,388, as well as taxane.

[0026] The present invention thus relates to the new2,4,5-trisubstituted pyrimidines of formula (I)

[0027] wherein

[0028] R_(a) denotes a hydrogen atom or an alkyl group,

[0029] R_(b) denotes an aralkyl group optionally substituted in thealkylene moiety by one or two alkyl groups, which may be substituted inthe aryl moiety by a carboxy, alkoxycarbonyl, aminocarbonyl,alkylaminocarbonyl, dialkylaminocarbonyl, amino, alkylamino,dialkylamino, cyano, trifluoromethyl or nitro group or one or twofluorine, chlorine, bromine or iodine atoms or one or two hydroxy, alkylor alkoxy groups, while the substituents may be identical or different,or by a 5- to 7-membered alkyleneimino group, while in each case one ortwo methylene groups adjacent to the nitrogen atom may be replaced ineach case by a carbonyl group or in the abovementioned 6- to 7-memberedalkyleneimino groups a methylene group in the 4-position may be replacedby an oxygen atom, by an imino, N-aryl-imino or N-alkyl-imino group, or

[0030] denotes a phenyl group optionally substituted by the groups R₁ toR₃, while

[0031] R₁ and R₂ in each case independently of one another denote

[0032] a fluorine, chlorine, bromine or iodine atom, or

[0033] a C₁₋₂-alkyl or hydroxy group,

[0034] a C₃₋₇-cycloalkyl or C₄₋₇-cycloalkoxy group which may besubstituted in each case

[0035] by one or two alkyl groups or by an aryl group,

[0036] a C₂₋₅-alkenyl group optionally substituted by an aryl group,

[0037] a C₂₋₅-alkynyl group optionally substituted by an aryl group

[0038] an aryl, aryloxy, aralkyl, aralkoxy, alkylsulphenyl,alkylsulphinyl, alkylsulphonyl, alkylsulphonyloxy,trifluoromethylsulphenyl, trifluoromethylsulphinyl,trifluoromethylsulphonyl, arylsulphenyl, arylsulphinyl, arylsulphonyl,aralkylsulphenyl, aralkylsulphinyl or aralkylsulphonyl group, a methylor methoxy group substituted by 1 to 3 fluorine atoms, a C₂₋₄-alkyl orC₂₋₄-alkoxy group substituted by 1 to 5 fluorine atoms, a nitro, amino,alkylamino, dialkylamino, C₃₋₇-cycloalkylamino,N-alkyl-C₃₋₇-cycloalkylamino, arylamino, N-alkyl-arylamino, aralkylaminoor N-alkyl-aralkylamino group,

[0039] a 4- to 7-membered alkyleneimino group optionally substituted by1 to 4 alkyl groups, while in the abovementioned 5- to 7-memberedalkyleneimino groups in each case one or two methylene groups adjacentto the nitrogen atom may be replaced in each case by a carbonyl group orin the abovementioned 6- to 7-membered alkyleneimino groups a methylenegroup in the 4-position may be replaced by an oxygen or sulphur atom, bya sulphinyl, sulphonyl, imino, N-alkylimino, N-alkylcarbonyl-imino,N-alkylsulphonyl-imino, N-arylcarbonyl-imino, N-arylsulphonyl-imino,N-aryl-imino or N-aralkyl-imino group, an (alkyleneimino)carbonyl or(alkyleneimino)sulphonyl group with in each case 4 to 7 cyclic atoms inthe alkyleneimino moiety, optionally substituted by 1 to 4 alkyl groups,while in the abovementioned 6- to 7-membered alkyleneimino moieties ineach case a methylene group in the 4-position may be replaced by anoxygen or sulphur atom, by a sulphinyl, sulphonyl, imino, N-alkyl-imino,N-alkylcarbonyl-imino, N-alkylsulphonyl-imino, N-arylcarbonyl-imino,N-arylsulphonyl-imino, N-aryl-imino or N-aralkyl-imino group,

[0040] an alkylcarbonylamino, N-alkyl-alkylcarbonylamino,alkyl-sulphonylamino, N-alkyl-alkylsulphonylamino, arylcarbonylamino,N-alkyl-arylcarbonylamino, arylsulphonylamino,N-alkyl-arylsulphonylamino, aralkylcarbonylamino,N-alkyl-aralkylcarbonylamino, aralkylsulphonylamino,N-alkyl-aralkylsulphonylamino, perfluoroalkylsulphonylamino,N-alkyl-perfluoralkylsulphonylamino, alkylcarbonyl, arylcarbonyl,aralkylcarbonyl, aryl-hydroxymethyl, aralkyl-hydroxymethyl, carboxy,alkoxycarbonyl, aralkoxycarbonyl, aminocarbonyl, alkylaminocarbonyl,dialkylaminocarbonyl, arylaminocarbonyl, N-alkyl-arylaminocarbonyl,aralkylaminocarbonyl, N-alkyl-aralkylaminocarbonyl,N-hydroxy-aminocarbonyl, N-hydroxy-alkylaminocarbonyl,N-alkoxy-aminocarbonyl, N-alkoxy-alkylaminocarbonyl, cyano, azido,N-cyano-amino or N-cyano-alkylamino group,

[0041] a sulpho, alkoxysulphonyl, aminosulphonyl, alkylaminosulphonyl,dialkylaminosulphonyl, arylaminosulphonyl, pyridylaminosulphonyl,pyrimidinylaminosulphonyl, N-alkyl-arylaminosulphonyl,aralkylaminosulphonyl or N-alkyl-aralkylaminosulphonyl group,

[0042] a phosphono, O-alkyl-phosphono, O,O′-dialkyl-phosphono,O-aralkyl-phosphono or O,O′-diaralkyl-phosphono group,

[0043] a C₁₋₂ alkyl group substituted by R₄, wherein

[0044] R₄ denotes a hydroxy, alkoxy, aryloxy, aralkoxy, amino,alkylamino, haloalkylamino, dialkylamino, alkylsulphenyl,alkylsulphinyl, alkylsulphonyl, arylsulphenyl, arylsulphinyl,arylsulphonyl, aralkylsulphenyl, aralkylsulphinyl, aralkylsulphonyl,carboxy, alkoxycarbonyl, aminocarbonyl, alkylaminocarbonyl,dialkylaminocarbonyl or cyano group,

[0045] a 4- to 7-membered alkyleneimino group optionally substituted by1 to 4 alkyl groups, while in the abovementioned 5- to 7-memberedalkyleneimino groups one or two methylene groups adjacent to thenitrogen atom may be replaced in each case by a carbonyl group or in theabovementioned 6- to 7-membered alkyleneimino groups a methylene groupin the 4-position may be replaced by an oxygen or sulphur atom, by asulphinyl, sulphonyl, imino, N-alkyl-imino, N-alkylcarbonyl-imino,N-alkylsulphonyl-imino, N-arylcarbonyl-imino, N-arylsulphonyl-imino,N-aryl-imino or N-aralkyl-imino group, or

[0046] a 4- to 7-membered alkyleneimino group optionally substituted by1 to 4 alkyl groups, while in the abovementioned 5- to 7-memberedalkyleneimino groups in each case one or two methylene groups adjacentto the nitrogen atom may be substituted by a carbonyl group or in theabovementioned 6- to 7-membered alkyleneimino groups may be substitutedby one or two hydroxy, alkoxy, aminocarbonyl, alkylaminocarbonyl,dialkylaminocarbonyl, amino, alkylamino and dialkylamino group,

[0047] an (alkyleneimino)carbonyl group optionally substituted by 1 to 4alkyl groups with 4 to 7 cyclic atoms in the alkyleneimino moiety ineach case, while in the abovementioned 6- to 7-membered alkyleneiminomoieties in each case a methylene group may be replaced in the4-position by an oxygen or sulphur atom, by a sulphinyl, sulphonyl,imino, N-alkyl-imino, N-alkylcarbonyl-imino, N-alkylsulphonyl-imino,N-arylcarbonyl-imino, N-arylsulphonyl-imino, N-aryl-imino orN-aralkyl-imino group, or

[0048] a group of formula

[0049]  wherein

[0050] h and k, which may be identical or different, represent thenumbers 1 to 3 or h denotes the number 0 and k denotes the number 2, 3or 4, while additionally the above benzo moiety may be mono- ordisubstituted by fluorine, chlorine, bromine or iodine atoms, by alkyl,trifluoromethyl, hydroxy, alkoxy, carboxy or cyano groups, while thesubstituents in each case may be identical or different, and the abovesaturated cyclic alkyleneimino moiety may be substituted by 1 or 2 alkylgroups,

[0051] R₃ denotes a fluorine, chlorine or bromine atom, a C₁₋₂ alkyl,C₁₋₂ alkoxy or trifluoromethyl group, or

[0052] a 5 or 6-membered heterocyclic, aromatic ring with at least onenitrogen atom and optionally a sulphur or oxygen atom which may besubstituted by one or two alkyl, aryl or aralkyl groups, or

[0053] a sulpho, alkoxysulphonyl, aminosulphonyl, alkylaminosulphonyl,dialkylaminosulphonyl, arylaminosulphonyl, pyridylaminosulphonyl,pyrimidinylaminosulphonyl, N-alkyl-arylaminosulphonyl,aralkylaminosulphonyl or N-alkyl-aralkylaminosulphonyl group,

[0054] R₂ together with R₃, if they are bound to adjacent carbon atoms,denote

[0055] a methylenedioxy group optionally substituted by one or two alkylgroups, or

[0056] an n-C₃₋₆-alkylene group optionally substituted by one or twoalkyl groups, wherein a methylene group may be replaced by an oxygen orsulphur atom, by a sulphinyl, sulphonyl, N-alkylcarbonyl-imino,N-alkylsulphonyl-imino, N-arylcarbonyl-imino or N-arylsulphonyl-iminogroup, or

[0057] a 1,3-butadien-1,4-diylene group optionally substituted by one ortwo fluorine, chlorine, bromine or iodine atoms, by one or two hydroxy,alkyl, alkoxy, trifluoromethyl, carboxy, alkoxycarbonyl, aminocarbonyl,alkylaminocarbonyl, dialkylaminocarbonyl or cyano groups, while thesubstituents may be identical or different, or

[0058] a group of formula

CH₂)_(m)—N(R₅)—(CH₂)_(n)—,

[0059]  wherein

[0060] the methylene groups of the cyclic alkyleneimino moieties thusformed may additionally be substituted by 1 or 2 alkyl groups,

[0061] R₅ denotes a hydrogen atom or an alkyl, haloalkyl, aryl oraralkyl group, and

[0062]  m and n, which may be identical or different, represent thenumbers 1, 2 or 3, while in the alkyleneimino moieties thus formed oneor two methylene groups adjacent to the nitrogen atom may be replaced ineach case by a carbonyl group, or

[0063]  m denotes the number 0 and n denotes the number 2, 3 or 4, whilein the alkyleneimino moieties thus formed in each case the methylenegroup adjacent to the nitrogen atom may be replaced by a carbonyl group,or

[0064]  R₂ together with R₃ denotes a group of formula —NH—C(═O)—(CH₂)—,—NH—C(═O)—(CH₂)₂, —NH—N═N, —NH—N═CH, —NH—CH═N—, —O—CH═N, —S—CH═N or—NH—CH═CH— and the tautomers of the ring systems defined by —NH—N═N,—NH—N═CH, —NH—CH═N—, while each hydrogen atom may be substituted by analkyl, aryl or aralkyl group, or

[0065] R_(a) together with R₁, if R₁ is in the o-position to thenitrogen atom substituted by R_(a), also denote an n-C₂₋₄-alkylene groupoptionally substituted by one or two alkyl groups, and

[0066] R_(c)NR_(d) denotes a 4- to 8-membered alkyleneimino groupoptionally substituted by 1 to 4 alkyl groups or 1 to 2 aryl groups,which is additionally substituted by the group R6, while

[0067] R₆ denotes a carboxy, alkoxycarbonyl, aminocarbonyl,alkylaminocarbonyl, dialkylaminocarbonyl, cyano, hydroxy, alkoxy,aryloxy, aralkoxy, alkylcarbonyloxy, arylcarbonyloxy, amino, alkylamino,hydroxy-C₂₋₄-alkylamino, dialkylamino, cyanamino, formylamino,N-(alkyl)-N-(hydroxy-C₂₋₄-alkyl)amino, bis-(hydroxy-C₂₋₄-alkyl)-aminogroup, alkylsulphenyl, alkylsulphinyl, alkylsulphonyl, arylsulphenyl,arylsulphinyl, arylsulphonyl, aralkylsulphenyl, aralkylsulphinyl,aralkylsulphonyl,

[0068]  an alkylcarbonylamino, N-alkyl-alkylcarbonylamino,alkylsulphonylamino, N-alkyl-alkylsulphonylamino, arylcarbonylamino,N-alkyl-arylcarbonylamino, arylsulphonylamino,N-alkyl-arylsulphonylamino, aralkylcarbonylamino,N-alkyl-aralkylcarbonylamino, aralkylsulphonylamino,N-alkyl-aralkylsulphonylamino, alkoxycarbonylamino,N-alkyl-alkoxycarbonylamino, alkoxycarbonylalkylamino,N-(alkyl)-N-(alkoxycarbonylalkyl)-amino, aralkoxycarbonylamino orN-alkyl-aralkoxycarbonylamino group,

[0069] an (NR₈R₉)CONR₇ or (NR₈R₉)SO2NR₇-group, wherein

[0070] R₇, R₈ and R₉, which may be identical or different, in each casedenote a hydrogen atom or an alkyl, aryl or pyridyl group, or

[0071] R₇ and R₈ together denote an n-C₂₋₄-alkylene group and R₉ denotesa hydrogen atom or an alkyl, aryl or pyridyl group,

[0072] an (alkyleneimino)carbonyl group optionally substituted by 1 to 4alkyl groups with in each case 4 to 7 cyclic atoms in the alkyleneiminomoiety, while in the abovementioned 6- to 7-membered alkyleneiminomoieties in each case a methylene group in the 4-position may bereplaced by an oxygen or sulphur atom, by a sulphinyl, sulphonyl, imino,N-alkyl-imino, N-alkylcarbonyl-imino, N-alkylsulphonyl-imino,N-aryl-imino or N-aralkyl-imino group,

[0073] a 4- to 7-membered alkyleneimino group optionally substituted by1 to 4 alkyl groups or a hydroxyalkyl group, while in the abovementioned5- to 7-membered alkyleneimino groups in each case one or two methylenegroups adjacent to the nitrogen atom may be replaced by a carbonylgroup,

[0074] a 6 or 7-membered alkyleneimino group optionally substituted by 1to 4 alkyl groups or a hydroxyalkyl group, while in each case amethylene group in the 4-position of the alkyleneimino moiety isreplaced by an oxygen or sulphur atom, by a carbonyl, sulphinyl,sulphonyl, imino, N-alkylimino, N-alkylcarbonyl-imino,N-alkylsulphonyl-imino, N-arylimino or N-aralkyl-imino group andadditionally in the alkyleneimino moiety of the abovementioned groups ineach case one or two of the methylene groups adjacent to the nitrogenatoms may be replaced by a carbonyl group,

[0075] a 4- to 7-membered alkyleneimino group substituted by a hydroxy,alkoxy, amino, alkylamino, dialkylamino, alkylcarbonylamino,N-alkyl-alkylcarbonylamino, alkylsulphonylamino,N-alkyl-alkylsulphonylamino, carboxy, alkoxycarbonyl, aminocarbonyl,alkylaminocarbonyl or dialkylaminocarbonyl group,

[0076] an alkyl group substituted by a carboxy, alkoxycarbonyl,aminocarbonyl, alkylaminocarbonyl or dialkylaminocarbonyl, cyano,hydroxy, alkoxy, aryloxy, amino, alkylamino, dialkylamino,alkylcarbonylamino, N-alkyl-alkylcarbonylamino, alkoxycarbonylamino,N-alkyl-alkoxycarbonylamino, alkylsulphonylamino,N-alkyl-alkylsulphonylamino, arylcarbonylamino,N-alkyl-arylcarbonylamino, arylsulphonylamino,N-alkyl-arylsulphonylamino, aminocarbonylalkylamino,N-(alkyl)-N-(aminocarbonylalkyl)-amino, alkylaminocarbonylalkylamino,N-(alkyl)-N-(alkylaminocarbonylalkyl)-amino,dialkylaminocarbonylalkylamino,N-(alkyl)-N-(dialkylaminocarbonylalkyl)-amino, dialkylaminoalkoxy,alkylsulphenyl, alkylsulphinyl, alkylsulphonyl, arylsulphenyl,arylsulphinyl or arylsulphonyl group, an (alkyleneimino)alkyl groupoptionally substituted by 1 to 4 alkyl groups with in each case 4 to 7cyclic atoms in the alkyleneimino moiety, while in the abovementioned 6-to 7-membered alkyleneimino moieties a methylene group in the 4-positionmay be replaced in each case by an oxygen or sulphur atom, by asulphinyl, sulphonyl, imino, N-alkyl-imino or N-alkylcarbonyl-iminogroup,

[0077] an (alkyleneimino)carbonylalkyl group optionally substituted by 1to 4 alkyl groups with in each case 4 to 7 cyclic atoms in thealkyleneimino moiety, while in the abovementioned 6- to 7-memberedalkyleneimino moieties a methylene group in the 4-position may bereplaced in each case by an oxygen or sulphur atom, by a sulphinyl,sulphonyl, imino or N-alkyl-imino group, a (carboxyalkyl)oxy,(alkoxycarbonylalkyl)oxy, (aminocarbonylalkyl)oxy,(alkylaminocarbonylalkyl)oxy or (dialkylaminocarbonylalkyl)oxy group,

[0078] an [(alkyleneimino)carbonylalkyl]oxy-group optionally substitutedby 1 to 4 alkyl groups with in each case 4 to 7 cyclic atoms in thealkyleneimino moiety, while in the abovementioned 6- to 7-memberedalkyleneimino moieties a methylene group in the 4-position may bereplaced in each case by an oxygen or sulphur atom, by a sulphinyl,sulphonyl, imino or N-alkyl-imino group,

[0079] a C₅₋₇-cycloalkyl group wherein a methylene group is replaced byan oxygen or sulphur atom, by a sulphinyl, sulphonyl, imino orN-alkyl-imino, alkylcarbonylimino or alkylsulphonylimino group,

[0080] a 3,4-dihydro-1H-quinazolin-2-on-3-yl or1H-benzimidazol-2-on-1-yl-group optionally substituted in the arylmoiety by one or two fluorine, chlorine, bromine or iodine atoms or oneor two nitro, alkyl, alkoxy or cyano groups in each case, while thesubstituents may be identical or different, or

[0081] R_(c)NR_(d) denotes a 6- to 8-membered alkyleneimino groupoptionally substituted by 1 to 4 alkyl groups or by an aryl group, whichmay additionally be substituted by the group R6, while in theabovementioned alkyleneimino groups a methylene group in the 4-positionis replaced by an oxygen or sulphur atom, by a carbonyl, sulphinyl,sulphonyl, N-oxido-N-alkylimino or R₁₀N-group in each case, while

[0082] R₁₀ denotes a hydrogen atom, an alkyl, hydroxy-C₂₋₄-alkyl,alkoxy-C₂₋₄-alkyl, amino-C₂₋₄-alkyl, alkylamino-C₂₋₄-alkyl,dialkylamino-C₂₋₄-alkyl, (hydroxy-C₂₋₄-alkoxy)-C₂₋₄-alkyl,aminocarbonylalkyl, alkylaminocarbonylalkyl, dialkylaminocarbonylalkyl,aryl, formyl, alkylcarbonyl, alkylsulphonyl, arylcarbonyl,aryl-sulphonyl, aralkylcarbonyl, aralkylsulphonyl, alkoxycarbonyl,aralkoxycarbonyl, cyano, aminocarbonyl, alkylaminocarbonyl ordialkylaminocarbonyl group, an amino-alkylcarbonyl,alkylamino-alkylcarbonyl, dialkylamino-alkylcarbonyl group,

[0083]  an alkyl group substituted by one, two or three aryl groups, an8-alkyl-8-aza-bicyclo[3.2.1]oct-3-yl group,

[0084] an aryl or a 2-, 3- or 4-pyridyl group or 2-, 4- or 5-pyrimidinylgroup an (alkyleneimino)carbonyl or (alkyleneimino)carbonylalkyl groupwith 4 to 7 cyclic atoms in the alkyleneimino moiety in each case, whilein the abovementioned 6- to 7-membered alkyleneimino moieties amethylene group in the 4-position may be replaced in each case by anoxygen or sulphur atom, by a sulphinyl, sulphonyl, imino, N-alkyl-imino,N-alkylcarbonyl-imino or N-aralkyl-imino group, or

[0085] R_(c)NR_(d) denotes a 3-thiazolidinyl-group substituted in the4-position by a carboxy, alkoxycarbonyl, aminocarbonyl,alkylaminocarbonyl, dialkylaminocarbonyl group, or

[0086] R_(c)NR_(d) denotes a 1-pyrrolidinyl group optionally substitutedby 1 to 4 alkyl groups, wherein two hydrogen atoms on the carbonskeleton are replaced by a straight-chain alkylene bridge, this bridgecontaining 2 to 6 carbon atoms if the two hydrogen atoms are located onthe same carbon atom, or 1 to 5 carbon atoms if the two hydrogen atomsare located on adjacent carbon atoms, or 2 to 4 carbon atoms if the twohydrogen atoms are located on carbon atoms separated by one atom, whilethe above-mentioned 1-pyrrolidinyl groups are additionally substitutedby the group R₆, which is as hereinbefore defined,

[0087] a 1-piperidinyl or 1-azacyclohept-1-yl group optionallysubstituted by 1 to 4 alkyl groups, wherein two hydrogen atoms on thecarbon skeleton are replaced by a straight-chain alkylene bridge, thisbridge containing 2 to 6 carbon atoms if the two hydrogen atoms arelocated on the same carbon atom, or 1 to 5 carbon atoms if the twohydrogen atoms are located on adjacent carbon atoms, or 1 to 4 carbonatoms if the two hydrogen atoms are located on carbon atoms separated byan atom, or 1 to 3 carbon atoms if the two hydrogen atoms are located oncarbon atoms separated by two atoms, while the abovementioned1-piperidinyl- and 1-azacyclohept-1-yl groups are additionallysubstituted by the group R6, which is as hereinbefore defined,

[0088] a 1-pyrrolidinyl group optionally substituted by 1 to 4 alkylgroups, wherein two hydrogen atoms in the 3 position are substituted bya —O—CH₂CH₂—O or —O—CH₂CH₂CH₂—O-group,

[0089] a 1-piperidinyl or 1-azacyclohept-1-yl group optionallysubstituted by 1 to 4 alkyl groups, wherein in the 3 position or in the4 position two hydrogen atoms are substituted by a —O—CH₂CH₂—O or—O—CH₂CH₂CH₂—O-group in each case,

[0090] a 1-azetidinyl group optionally substituted by an alkyl group,wherein the two hydrogen atoms of a methylene group are replaced by astraight-chain C₄₋₆-alkylene bridge, while in each case a methylenegroup in the C₄₋₆-alkylene bridge is replaced by a R₁₀N-group, where R₁₀is as hereinbefore defined, while the bicyclic ring thus formed mayadditionally be substituted by a hydroxy, alkoxy, amino, alkylamino,dialkylamino, cyano, alkylcarbonylamino, alkylsulphonylamino,alkoxycarbonylamino, arylcarbonyl, carboxy, alkoxycarbonyl,aminocarbonyl, alkylaminocarbonyl or dialkylaminocarbonyl group,

[0091] a 1-pyrrolidinyl, 1-piperidinyl or 1-azacyclohept-1-yl groupoptionally substituted by 1 to 2 alkyl groups, wherein the two hydrogenatoms of a methylene group are replaced by a straight-chainC₃₋₆-alkylene bridge, while in each case a methylene group in theC₃₋₆-alkylene bridge is replaced by a R₁₀N-group, while R₁₀ is ashereinbefore defined, while the bicyclic ring thus formed mayadditionally be substituted by a hydroxy, alkoxy, amino, alkylamino,dialkylamino, cyano, alkylcarbonylamino, alkylsulphonylamino,alkoxycarbonylamino, arylcarbonyl, carboxy, alkoxycarbonyl,aminocarbonyl, alkylaminocarbonyl or dialkylaminocarbonyl group,

[0092] a group of the structure

[0093]  optionally substituted in the alkylene moieties by 1 or 2 alkylgroups, wherein

[0094] p and q, which may be identical or different, represent thenumber 1 or 2, and

[0095] the unit —V═W—X═Y— denotes one of the groups (a), (b), (c), (d)or (e): —N═C—C═C— (a), —C═N—C═C— (b), —C═N—N═C— (c), —N═C—C═N— (d),—N═C—N═C— (e),

[0096] or —V═W— taken together represent an oxygen or sulphur atom and—X═Y— represents one of the groups —N═C, —C═N or —C═C—,

[0097] or —V═W— taken together represent an imino, N-alkyl-imino,N-aralkyl-imino or N-aryl-imino group and —X═Y— represents one of thegroups —N═N, —N═C, —C═N or —C═C—,

[0098] or, if p and q are not the same,

[0099] —X═Y— taken together represent an oxygen or sulphur atom and—V═W— represents one of the groups —N═C, —C═N or —C═C—,

[0100] or —X═Y— taken together represent an imino, N-alkyl-imino,N-aralkyl-imino or N-aryl-imino-group and —V═W— represents one of thegroups —N═N, —N═C, —C═N or —C═C—,

[0101] while one or two of the available carbon atoms of the unit—V═W—X═Y— may be substituted in each case by a hydroxy, alkoxy, amino,alkylamino, dialkylamino, carboxy, alkoxycarbonyl, aminocarbonyl,alkylaminocarbonyl, dialkylaminocarbonyl or hydrazinocarbonyl group,while the substituents may be identical or different, and the remainingavailable carbon atoms of the unit —V═W—X═Y— are substituted by ahydrogen atom, an alkyl, aralkyl or aryl group, or

[0102] R_(c) denotes a hydrogen atom or a C₁₋₈-alkyl group,

[0103] a C₃₋₇-cycloalkyl, C₃₋₇-cycloalkyl-alkyl or aralkyl group whichmay be substituted in each case by one or two alkyl groups or by an arylgroup,

[0104] an alkyl group which is substituted

[0105] by a hydroxy, alkoxy, aryloxy, aralkoxy, alkylsulphenyl,alkylsulphinyl, alkylsulphonyl, arylsulphenyl, arylsulphinyl,arylsulphonyl, amino, alkylamino, dialkylamino, alkylcarbonylamino,N-alkyl-alkylcarbonylamino, alkylsulphonylamino,N-alkyl-alkylsulphonylamino, trifluoromethylsulphonylamino,N-alkyl-trifluoromethylsulphonylamino, carboxy, alkoxycarbonyl,aralkoxycarbonyl, aminocarbonyl, alkylaminocarbonyl,dialkylaminocarbonyl, cyano group,

[0106] by a 2-, 3- or 4-pyridyl group,

[0107] by an alkyleneimino or (alkyleneimino)carbonyl group with in eachcase 4 to 7 cyclic atoms in the alkyleneimino moiety, optionallysubstituted by 1 to 4 alkyl groups, while in the abovementioned 6- to7-membered alkyleneimino groups a methylene group may be replaced in the4-position by an oxygen or sulphur atom, by an imino, N-alkyl-imino,N-aryl-imino, N-aralkyl-imino, N-arylcarbonyl-imino orN-alkylcarbonyl-imino group,

[0108] a C₃₋₅-alkenyl group optionally substituted by an aryl group,while the vinyl moiety may not be attached to the nitrogen atom of theRcNRd group,

[0109] a C₃₋₅-alkynyl group optionally substituted by an aryl group,while the ethynyl moiety may not be attached to the nitrogen atom of theR_(c)NR_(d) group, and

[0110] R_(d) denotes a C₁₋₁₆-alkyl group which is substituted by a groupselected from the groups (a) to (n):

[0111] (a) a carboxy, alkoxycarbonyl, aminocarbonyl, alkylaminocarbonyl,dialkylaminocarbonyl, hydroxy-C₂₋₄-alkylaminocarbonyl, cyano, hydroxy,alkoxy, aryloxy, aralkoxy, C₂₋₄-alkylenedioxy, alkylcarbonyloxy,arylcarbonyloxy, formylamino, alkylcarbonylamino, arylcarbonylamino,amino, alkylamino, dialkylamino, naphthylamino, aralkylamino,diaralkylamino or N-alkyl-aralkylamino group,

[0112] (b) a phenylamino, N-alkyl-N-phenylamino, pyridylamino orN-alkyl-N-pyridylamino group optionally substituted in the aryl moietyby one or two fluorine, chlorine, bromine or iodine atoms or one or twonitro, trifluoromethyl, alkyl, hydroxy, alkoxy, amino, alkylamino,dialkylamino, carboxy, alkoxycarbonyl, aminocarbonyl,alkylaminocarbonyl, dialkylaminocarbonyl or cyano groups, while thesubstituents may be identical or different,

[0113] (c) an alkoxy group substituted by one, two or three aryl groups,

[0114] (d) a hydroxy-C₂₋₄-alkylaminocarbonyl,alkoxy-C₂₋₄-alkylaminocarbonyl, amino-C2-4-alkylaminocarbonyl,alkylamino-C₂₋₄-alkylaminocarbonyl,dialkylamino-C₂₋₄-alkylaminocarbonyl, carboxyalkylaminocarbonyl,alkoxycarbonylalkylaminocarbonyl, aminocarbonylalkylaminocarbonyl,alkylaminocarbonylalkylaminocarbonyl,dialkylaminocarbonylalkylaminocarbonyl, arylaminocarbonyl,N-alkyl-arylaminocarbonyl, aralkylaminocarbonyl,N-alkyl-aralkylaminocarbonyl,

[0115] (e) a group of formula —C(═NH)NH₂ or —NH—C(═NH)NH₂, which isoptionally substituted by a cyano or alkoxycarbonyl group,

[0116] (f) an (alkyleneimino)carbonyl group optionally substituted by 1to 4 alkyl groups with in each case 4 to 7 cyclic atoms in thealkyleneimino moiety, while in a 6 or 7-membered alkyleneimino moiety amethylene group in the 4-position may be replaced in each case by anoxygen or sulphur atom, by a sulphinyl, sulphonyl, imino, N-alkyl-imino,N-alkylcarbonyl-imino, N-alkylsulphonyl-imino, N-aryl-imino orN-aralkyl-imino group,

[0117] (g) a 4- to 7-membered alkyleneimino group optionally substitutedby 1 to 4 alkyl groups, while in the abovementioned 6 or 7-memberedalkyleneimino groups a methylene group in the 4-position may be replacedin each case by an oxygen or sulphur atom, by a sulphinyl, sulphonyl orR₁₀N group, where R₁₀ is as hereinbefore defined, and additionally inthe abovementioned 5- to 7-membered alkyleneimino groups in each caseone or two methylene groups adjacent to the nitrogen atoms may bereplaced by a carbonyl group,

[0118] (h) a 5- to 7-membered alkyleneimino group optionally substitutedby 1 to 2 alkyl groups which is substituted by a hydroxyalkyl,aminoalkyl, alkylaminoalkyl or dialkylaminoalkyl group,

[0119] (i) an alkylsulphonylamino, N-alkyl-alkylsulphonylamino,arylcarbonylamino, N-alkyl-arylcarbonylamino, alkylcarbonylamino,N-alkyl-alkylcarbonylamino, arylsulphonylamino,N-alkyl-arylsulphonylamino, aralkylcarbonylamino,N-alkyl-aralkylcarbonylamino, alkoxyalkyl-carbonylamino,alkoxyalkyl-N-alkyl-carbonylamino, dialkylamino-alkylcarbonylamino,alkylamino-alkylcarbonylamino, amino-alkylcarbonylamino,aralkylsulphonylamino, N-alkyl-aralkylsulphonylamino,alkoxycarbonylamino, N-alkyl-alkoxycarbonylamino, aralkoxycarbonylaminoor N-alkyl-aralkoxycarbonylamino group,

[0120] (j) a (R₉NR₈)—CO—NR₇ or (R₉NR₈)—SO2-NR₇ group, where R₇, R₈ andR₉ are as hereinbefore defined,

[0121] (k) an alkylsulphenyl, alkylsulphinyl, alkylsulphonyl,arylsulphenyl, arylsulphinyl, arylsulphonyl, aralkylsulphenyl,aralkylsulphinyl or aralkylsulphonyl group,

[0122] (l) a C₄₋₇-cycloalkyl group substituted by R₆ and optionallyadditionally by 1 to 4 alkyl groups, where R₆ is as hereinbeforedefined,

[0123] (m) an C₅₋₇-cycloalkyl group optionally substituted by 1 to 4alkyl groups wherein a methylene group is replaced by an oxygen orsulphur atom, by a sulphinyl, sulphonyl or NR₁₀ group, where R₁₀ is ashereinbefore defined,

[0124] (n) a 4-piperidinyl-alkyl group optionally substituted by 1 to 4alkyl groups, which is substituted in the 1 position by R₁₀ andadditionally in the 4-position by a hydroxy group, where R10 is ashereinbefore defined, and wherein additionally hydrogen atoms inpositions 2 and 6 of the piperidinyl structure are together replaced bya C₂₋₃-alkylene bridge,

[0125] a methyl group substituted by a3-hydroxy-1,3-dihydro-indol-2-on-3-yl or2-aminocarbonyl-1,3-dihydro-isoindol-5-yl-group,

[0126] a group of the structure

[0127] substituted in the aryl moiety by a carboxy, alkoxycarbonyl,aminocarbonyl, alkylaminocarbonyl, dialkylaminocarbonyl, carboxyalkyl,alkoxycarbonylalkyl, aminocarbonylalkyl, alkylaminocarbonylalkyl ordialkylaminocarbonylalkyl group and optionally additionally substitutedin the alkylene moiety by 1 or 2 alkyl groups

[0128] wherein x and y, which may be identical or different,independently of one another represent the number 0, 1 or 2, but x and ytogether must yield at least the number 2,

[0129] a C₃₋₈-alkyl group substituted by a hydroxy group andadditionally by an amino, alkylamino, dialkylamino, hydroxy, alkoxy,1-pyrrolidinyl, 1-piperidinyl or morpholino group,

[0130] a C₂₋₈-alkyl group substituted by a carboxy group andadditionally by an amino, hydroxy, aminocarbonyl orbenzyloxycarbonylamino group,

[0131] a C₂₋₄-alkyl group which is substituted by a C₂₋₄-alkylsulphenylor C₂₋₄-alkoxy group, which is substituted in the ω-position by anamino, hydroxy or alkoxy group,

[0132] a C₂₋₄-alkyl group which is substituted by aC₂₋₄-alkoxy-C₂₋₄-alkoxy group, which is substituted in the ω-position byan amino or hydroxy group,

[0133] a cyclopropyl group which is substituted by a carboxy,alkoxycarbonyl, aminocarbonyl, alkylaminocarbonyl ordialkylaminocarbonyl group or by an (alkyleneimino)carbonyl groupoptionally substituted by 1 to 4 alkyl groups with 4 to 7 cyclic atomsin the alkyleneimino moiety in each case, while in the abovementioned 6or 7-membered alkyleneimino moieties a methylene group in the 4-positionmay be replaced in each case by an oxygen or sulphur atom, by asulphinyl, sulphonyl, imino, N-alkyl-imino, N-alkylcarbonyl-imino,N-alkylsulphonyl-imino, N-aryl-imino or N-aralkyl-imino group,

[0134] a C₄₋₇-cycloalkyl group optionally substituted by 1 to 4 alkylgroups, which is additionally substituted by R₆, which is ashereinbefore defined,

[0135] a C₅₋₇-cycloalkyl group optionally substituted by 1 to 2 alkylgroups which is additionally substituted by a N,N-dialkyl-N-oxido-aminogroup,

[0136] a C₄₋₇-cycloalkyl group optionally substituted by 1 to 4 alkylgroups which may additionally be substituted by R₆, while in thecycloalkyl moiety a methylene group is replaced by an oxygen or sulphuratom, by a sulphinyl, sulphonyl, N-alkyl-N-oxido-imino or R₁₀N group,where R₆ and R₁₀ are as hereinbefore defined,

[0137] a C₅-C₇-cycloalkyl or C₅-C₇-cycloalkylalkyl group optionallysubstituted by 1 to 4 alkyl groups, wherein in each case a methylenegroup in the cycloalkyl moiety is replaced by a carbonyl group,

[0138] a cyclopentyl or cyclopentylalkyl group optionally substituted by1 to 4 alkyl groups, wherein in each case two hydrogen atoms in thecyclopentyl moiety are replaced by a straight-chain alkylene bridge,this bridge containing 2 to 6 carbon atoms, if the two hydrogen atomsare located on the same carbon atom, or 1 to 5 carbon atoms, if the twohydrogen atoms are located on adjacent carbon atoms, or 2 to 4 carbonatoms if the two hydrogen atoms are located on carbon atoms separated bya carbon atom, while the abovementioned rings are additionallysubstituted by the group R6, which is as hereinbefore defined,

[0139] a cyclohexyl, cyclohexylalkyl, cycloheptyl or cycloheptylalkylgroup optionally substituted by 1 to 4 alkyl groups, wherein twohydrogen atoms in the cycloalkyl moiety are replaced by a straight-chainalkylene bridge in each case, this bridge containing 2 to 6 carbon atomsif the two hydrogen atoms are located on the same carbon atom, or 1 to 5carbon atoms if the two hydrogen atoms are located on adjacent carbonatoms, or 1 to 4 carbon atoms if the two hydrogen atoms are located oncarbon atoms separated by a carbon atom, or 1 to 3 carbon atoms if thetwo hydrogen atoms are located on carbon atoms separated by two carbonatoms, while the abovementioned rings are additionally substituted bythe group R₆, which is as hereinbefore defined,

[0140] an alkyl group substituted by a3-hydroxy-1,3-dihydro-indol-2-on-3-yl or2-aminocarbonyl-1,3-dihydro-isoindol-5-yl group,

[0141] a C₁₋₁₀-alkyl group substituted by an aryl group, while theabovementioned aryl moiety is substituted by an alkoxycarbonyl, carboxy,carboxyalkyl, aminosulphonyl, trifluoromethoxy, cyano, aminoalkyl,amino, alkylamino, dialkylamino, nitro, 2H-pyridazin-3-on-6-yl,hydroxyphenyl, hydroxyalkyl, hydroxy or alkoxy group,

[0142] an aralkyl group which is substituted in the aryl moiety by ahydroxy or alkoxy group and additionally by a carboxy, alkoxycarbonyl,hydroxy or alkoxy group,

[0143] a C₁₋₁₀-alkyl group substituted by a pyrrolyl, imidazolyl,pyrazolyl, pyridyl, pyrimidinyl, pyrazinyl, indolyl or benzimidazolylgroup, while the abovementioned heteroaryl moieties on the availablecarbon atoms may additionally be substituted in each case by one or twogroups selected from fluorine, chlorine, bromine or iodine atoms, alkyl,alkoxycarbonyl, carboxy, trifluoromethyl, trifluoromethoxy, cyano,amino, alkylamino, dialkylamino, nitro, hydroxy or alkoxy groups, whilethe substituents may be identical or different,

[0144] a C₁₋₁₀-alkyl group substituted by a carboxy, alkoxycarbonyl,aminocarbonyl, alkylaminocarbonyl, dialkylaminocarbonyl,aralkylaminocarbonyl, cyano, hydroxy, alkoxy, aryloxy, amino,alkylamino, dialkylamino, alkylcarbonylamino or alkoxycarbonylaminogroup, which is additionally substituted by one or two aryl groups or apyrrolyl, imidazolyl, pyrazolyl, pyridyl, pyrimidinyl, pyrazinyl,indolyl or benzimidazolyl group, while the abovementioned aryl orheteroaryl moieties at the available carbon atoms may additionally besubstituted in each case by one or two groups selected from fluorine,chlorine, bromine or iodine atoms, alkyl, alkoxycarbonyl, carboxy,trifluoromethyl, trifluoromethoxy, cyano, amino, alkylamino,dialkylamino, nitro, hydroxy or alkoxy groups, while the substituentsmay be identical or different,

[0145] a C₁₋₆-alkyl group substituted by an aryl group which issubstituted in the aryl moiety by a hydroxy or amino group andadditionally by two fluorine, chlorine, bromine or iodine atoms, whilethe substituents may be identical or different,

[0146] a C₂₋₆-alkyl group substituted by a carboxy or alkoxycarbonylgroup, which is additionally substituted by an amino, alkylamino,dialkylamino, alkylcarbonylamino, N-alkyl-alkylcarbonylamino,alkylsulphonylamino, N-alkyl-alkylsulphonylamino, arylcarbonylamino,N-alkyl-arylcarbonylamino, arylsulphonylamino,N-alkyl-arylsulphonylamino, aralkylcarbonylamino,N-alkyl-aralkylcarbonylamino, aralkylsulphonylamino,N-alkyl-aralkylsulphonylamino, alkoxycarbonylamino,N-alkyl-alkoxycarbonylamino, aralkoxycarbonylamino orN-alkyl-aralkoxycarbonylamino group, a 3-quinuclidinyl, 4-quinuclidinyl,2-quinuclidinyl-alkyl,

[0147]3-quinuclidinyl-alkyl or 4-quinuclidinyl-alkyl group, or

[0148] R_(c) denotes a hydrogen atom or an alkyl group and R_(d) denotesa hydroxy or alkoxy group, and

[0149] R_(e) denotes a fluorine, chlorine, bromine or iodine atom,

[0150] a cyano, nitro, alkyl, alkoxy, dialkylamino, alkylamino,alkylcarbonyl, alkylsulphenyl, alkylsulphinyl, alkylsulphonyl,alkoxyalkyl-alkylcarbonyl-N-alkyl-aminoalkyl, alkylcarbonyl-aminoalkyl,alkylsulphonyl-aminoalkyl, aminocarbonyl, alkylaminocarbonyl,dialkylaminocarbonyl, aminoalkyl, alkylaminoalkyl or dialkylaminoalkylgroup,

[0151] a methyl, methylsulphenyl or methoxy group substituted by 1 to 3fluorine atoms,

[0152] a C₂₋₄-alkyl, C₂₋₄-alkylsulphenyl or C₂₋₄-alkoxy groupsubstituted by 1 to 5 fluorine atoms,

[0153] an C₃₋₆-cycloalkyl-C₁₋₃-alkyl group optionally substituted by 1-6fluorine atoms,

[0154] a C₂₋₅-alkenyl or C₃₋₅-alkenyloxy group, while the vinyl moietymay not be attached to the oxygen atom,

[0155] a C₂₋₆-alkynyl or C₃₋₆-alkynyloxy group, while the ethynyl moietymay not be attached to the oxygen atom,

[0156] an alkyleneimino or alkyleneimino-alkyl group with in each case 4to 7 cyclic atoms in the alkyleneimino moiety optionally substituted by1 to 4 alkyl groups, while in a 6- or 7-membered alkyleneimino moiety amethylene group in the 4-position may be replaced in each case by anoxygen or sulphur atom, by a sulphinyl, sulphonyl, imino, N-alkyl-imino,N-alkylcarbonyl-imino, N-alkylsulphonyl-imino, N-aryl-imino orN-aralkyl-imino group,

[0157] optionally in the form of the tautomers, racemates, enantiomers,diastereomers and mixtures thereof, and optionally also thepharmacologically acceptable acid addition salts thereof,

[0158] while, unless otherwise stated,

[0159] by the aryl moieties mentioned in the definition of theabovementioned groups is meant a phenyl group, wherein one or two carbonatoms may be replaced by a nitrogen atom in each case, while theabovementioned aryl moieties in each case may be monosubstituted by R₁₁,mono-, di- or trisubstituted by R₁₂ or monosubstituted by R₁₁ andadditionally mono- or disubstituted by R₁₂, while the substituents maybe identical or different, and

[0160] R₁₁ denotes a cyano, carboxy, aminocarbonyl, alkylaminocarbonyl,dialkylaminocarbonyl, alkoxycarbonyl, alkylcarbonyl, alkylsulphenyl,alkylsulphinyl, alkylsulphonyl, alkylsulphonyloxy, perfluoroalkyl,perfluoroalkoxy, nitro, amino, alkylcarbonylamino,N-alkyl-alkylcarbonylamino, alkylamino, dialkylamino,hydroxy-C2-4-alkylamino, N-alkyl-(hydroxy-C2-4-alkyl)amino,bis-(hydroxy-C2-4-alkyl)amino, phenylalkylcarbonylamino,phenylcarbonylamino, alkylsulphonylamino, phenylalkylsulphonylamino,phenylsulphonylamino, N-alkyl-phenylalkylcarbonylamino,N-alkyl-phenylcarbonylamino, N-alkyl-alkylsulphonylamino,N-alkyl-phenylalkylsulphonylamino, N-alkyl-phenylsulphonylamino,aminosulphonyl, alkylaminosulphonyl, dialkylaminosulphonyl,(R₉NR₈)—CO—NR₇ or (R₉NR₈)—SO2-NR₇ group, where R₇, R₈ and R₉ are ashereinbefore defined,

[0161] a 5- to 7-membered alkyleneimino group optionally substituted by1 to 4 alkyl groups or a hydroxyalkyl group, while in the abovementioned6- to 7-membered alkyleneimino groups a methylene group in the4-position may be replaced in each case by an oxygen atom or an R₁₀Ngroup, where R₁₀ is as hereinbefore defined,

[0162] a 5- to 7-membered alkyleneimino group optionally substituted by1 to 4 alkyl groups or a hydroxyalkyl group, while in each case one ortwo methylene groups adjacent to the nitrogen atom is replaced by acarbonyl group in each case, and

[0163] R₁₂ denotes an alkyl, hydroxy or alkoxy group, a fluorine,chlorine, bromine or iodine atom, while two groups R₁₂, if they arebound to adjacent carbon atoms, may also denote an alkylene group with 3to 6 carbon atoms, a 1,3-butadien-1,4-diylene group or a methylenedioxygroup,

[0164] and, unless stated to the contrary, the abovementioned alkyl,alkylene and alkoxy moieties each contain 1 to 4 carbon atoms,

[0165] while, unless otherwise stated, each carbon atom in theabovementioned alkyl, alkylene or cycloalkylene moieties, which is boundto a nitrogen, oxygen or sulphur atom, cannot be bound to any otherhalogen, nitrogen, oxygen or sulphur atom.

[0166] Preferred compounds of formula I are those wherein

[0167] R_(a) denotes a hydrogen atom or an alkyl group,

[0168] R_(b) denotes an aralkyl group which may be substituted in thearyl moiety by a carboxy, alkoxycarbonyl, aminocarbonyl,alkylaminocarbonyl, dialkylaminocarbonyl, amino, alkylamino,dialkylamino, cyano, trifluoromethyl or nitro group or one or twofluorine, chlorine, bromine or iodine atoms or one or two hydroxy, alkylor alkoxy groups, while the substituents may be identical or different,or by a 5- to 7-membered alkyleneimino group, while in each case one ortwo methylene groups adjacent to the nitrogen atom may be replaced ineach case by a carbonyl group or in the abovementioned 6- to 7-memberedalkyleneimino groups a methylene group in the 4-position may be replacedby an oxygen atom, by an imino, N-aryl-imino or N-alkyl-imino group, andwherein the alkylene moiety of the abovementioned aralkyl groups may besubstituted by one or two alkyl groups, or

[0169] a phenyl group optionally substituted by the groups R₁ to R₃,

[0170] while

[0171] R₁ denotes a fluorine, chlorine, bromine or iodine atom,

[0172] a C₁₋₂-alkyl or hydroxy group,

[0173] a C₃₋₆-cycloalkyl or C₅₋₆-cycloalkoxy group,

[0174] a C₂₋₅-alkenyl group,

[0175] a C₂₋₅-alkynyl group,

[0176] an aryl, aryloxy, aralkyl, aralkoxy, alkylsulphenyl,alkylsulphinyl, alkylsulphonyl, alkylsulphonyloxy,trifluoromethylsulphenyl, trifluoromethylsulphonyl, arylsulphenyl,arylsulphinyl, arylsulphonyl, aralkylsulphenyl, aralkylsulphinyl oraralkylsulphonyl group,

[0177] a methyl or methoxy group substituted by 1 to 3 fluorine atoms,

[0178] a C₂₋₄-alkyl or C₂₋₄-alkoxy group substituted by 1 to 5 fluorineatoms,

[0179] a nitro, amino, alkylamino, dialkylamino, C₃₋₆-cycloalkylamino,N-alkyl-C₃₋₆-cycloalkylamino, arylamino, N-alkyl-arylamino, aralkylaminoor N-alkyl-aralkylamino group,

[0180] a 5- to 7-membered alkyleneimino group, while in each case one ortwo methylene groups adjacent to the nitrogen atom may be replaced ineach case by a carbonyl group or in the abovementioned 6- to 7-memberedalkyleneimino groups a methylene group in the 4-position may be replacedby an oxygen atom, by an imino, N-aryl-imino or N-alkyl-imino group andthe alkyleneimino groups may additionally be substituted by 1-2 methylgroups,

[0181] an (alkyleneimino)carbonyl or (alkyleneimino)sulphonyl group within each case 5 to 7 cyclic atoms in the alkyleneimino moiety, while inthe abovementioned 6- to 7-membered alkyleneimino moieties a methylenegroup in the 4-position may be replaced in each case by an oxygen atom,by an imino, N-aryl-imino or N-alkyl-imino group,

[0182] an alkylcarbonylamino, N-alkyl-alkylcarbonylamino,alkyl-sulphonylamino, N-alkyl-alkylsulphonylamino, arylcarbonylamino,N-alkyl-arylcarbonylamino, arylsulphonylamino,N-alkyl-arylsulphonylamino, aralkylcarbonylamino,N-alkyl-aralkylcarbonylamino, aralkylsulphonylamino,N-alkyl-aralkylsulphonylamino, trifluoromethylsulphonylamino,N-alkyl-trifluoromethylsulphonylamino, alkylcarbonyl, arylcarbonyl,aralkylcarbonyl, carboxy, alkoxycarbonyl, aminocarbonyl,alkylaminocarbonyl, dialkylaminocarbonyl, arylaminocarbonyl,N-alkyl-arylaminocarbonyl, aralkylaminocarbonyl,N-alkyl-aralkylaminocarbonyl, N-hydroxy-aminocarbonyl,N-hydroxy-alkylaminocarbonyl, N-alkoxy-aminocarbonyl,N-alkoxy-alkylaminocarbonyl, cyano, azido, N-cyano-amino orN-cyano-alkylamino group,

[0183] a sulpho, aminosulphonyl, alkylaminosulphonyl,dialkylaminosulphonyl, arylaminosulphonyl, pyridylaminosulphonyl,N-alkyl-arylaminosulphonyl, aralkylaminosulphonyl orN-alkyl-aralkylaminosulphonyl group, or

[0184] a C₁₋₂ alkyl group substituted by R₄,

[0185]  wherein

[0186] R₄ denotes a hydroxy, alkoxy, aryloxy, amino, alkylamino,fluoroalkylamino, dialkylamino, alkylsulphenyl, alkylsulphinyl,alkylsulphonyl, arylsulphenyl, arylsulphinyl, arylsulphonyl, carboxy,alkoxycarbonyl, aminocarbonyl, alkylaminocarbonyl, dialkylaminocarbonylor cyano group,

[0187] a 5- to 7-membered alkyleneimino group optionally substituted byone or two alkyl groups, while in the abovementioned 6- to 7-memberedalkyleneimino groups a methylene group in the 4-position may be replacedby an oxygen or sulphur atom, by an imino, N-alkyl-imino,N-alkylcarbonyl-imino, N-alkylsulphonyl-imino, N-arylcarbonyl-imino,N-arylsulphonyl-imino, N-aryl-imino or N-aralkyl-imino group, or may besubstituted by a hydroxy, alkoxy, aminocarbonyl, alkylaminocarbonyl,dialkylaminocarbonyl, amino, alkylamino- and dialkylamino group, or

[0188] an (alkyleneimino)carbonyl group with in each case 5 to 7 cyclicatoms in the alkyleneimino moiety optionally substituted by one or twoalkyl groups, while in the abovementioned 6- to 7-membered alkyleneiminomoieties a methylene group in the 4-position may be replaced in eachcase by an oxygen or sulphur atom, by an imino, N-alkyl-imino orN-alkylcarbonyl-imino group, or

[0189] a group of formula

[0190]  wherein

[0191] h and k, which may be identical or different, represent thenumbers 1 to 2 or

[0192] h denotes the number 0 and k denotes the number 2 or 3, whileadditionally the above benzo portion may be substituted by a fluorine,chlorine, bromine or iodine atom or by an alkyl, trifluoromethyl,hydroxy, alkoxy, carboxy or cyano group and the above saturated cyclicimino moiety may be substituted by 1 or 2 alkyl groups,

[0193] R₂ denotes a fluorine, chlorine or bromine atom, a C₁₋₂ alkyl,trifluoromethyl, hydroxy, amino, alkylamino, dialkylamino,alkylcarbonylamino, N-alkyl-alkylcarbonylamino, alkylsulphonylamino,N-alkyl-alkylsulphonylamino, trifluoromethylsulphonylamino,N-alkyl-trifluoromethylsulphonylamino or cyano group, and

[0194] R₃ denotes a fluorine, chlorine or bromine atom, a C₁₋₂ alky,trifluoromethyl or alkoxy group,

[0195] a group of the structure

[0196]  wherein the point of attachment may be a carbon or a nitrogenatom and up to three carbon atoms may be replaced by a nitrogen atom andthe ring may be substituted, via each of the atoms, by one or two alkyl,aryl or aralkyl groups, or

[0197] a sulpho, aminosulphonyl, alkylaminosulphonyl,dialkylaminosulphonyl, arylaminosulphonyl, pyridylaminosulphonyl,N-alkyl-arylaminosulphonyl, aralkylaminosulphonyl orN-alkyl-aralkylaminosulphonyl group

[0198] R₂ together with R₃, if they are bound to adjacent carbon atoms,denote

[0199] a methylenedioxy group optionally substituted by one or two alkylgroups, or an n-C₃₋₅-alkylene group optionally substituted by one or twoalkyl groups wherein a methylene group may be replaced by an oxygenatom, by an imino, N-alkyl-imino or N-aralkyl-imino group, or

[0200] a 1,3-butadiene-1,4-diylene group optionally substituted by afluorine, chlorine or bromine atom, by a hydroxy, alkyl, alkoxy,trifluoromethyl, carboxy or cyano group or

[0201] a group of formula —NH—C(═O)—(CH₂) or —NH—C(═O)—(CH₂)₂, which mayadditionally be substituted in the alkylene moiety by 1 or 2 alkylgroups, or a group of formula —NH—N═N, —NH—N═CH, —NH—CH═N—, —O—CH═N,—S—CH═N, —NH—CH═CH— and the tautomers thereof, while each hydrogen atommay be substituted by an alkyl, aryl or aralkyl group, or

[0202] a group of formula —(CH₂)_(m)—NR₅—(CH₂)_(n)—,

[0203] wherein m and n which may be identical or different in each caserepresent 1 or 2, and

[0204] R₅ denotes hydrogen, C₁₋₆ alkyl or C₁₋₆ fluoroalkyl, or

[0205] R_(a) together with R₁, if R1 is in the o-position to thenitrogen atom substituted by R_(a), also denote an n-C₂₋₃-alkylene groupoptionally substituted by one or two alkyl groups, and

[0206] R_(c)NR_(d) represents a 4- to 7-membered alkyleneimino groupoptionally substituted by 1 to 2 alkyl or aryl groups which isadditionally substituted by the group R₆, where

[0207] R₆ denotes a carboxy, alkoxycarbonyl, aminoalkyl, aminocarbonyl,alkylaminocarbonyl, dialkylaminocarbonyl, cyano, hydroxy, alkoxy,aryloxy, aralkoxy, alkylcarbonyloxy, arylcarbonyloxy, amino, alkylamino,hydroxy-C2-4-alkylamino, dialkylamino, cyanamino, formylamino,alkylsulphenyl, alkylsulphinyl, alkylsulphonyl, arylsulphenyl,arylsulphinyl, arylsulphonyl, aralkylsulphenyl, aralkylsulphinyl oraralkylsulphonyl group,

[0208] an alkylcarbonylamino, N-alkyl-alkylcarbonylamino,alkylsulphonylamino, N-alkyl-alkylsulphonylamino, arylcarbonylamino,N-alkyl-arylcarbonylamino, arylsulphonylamino,N-alkyl-arylsulphonylamino, aralkylcarbonylamino,N-alkyl-aralkylcarbonylamino, aralkylsulphonylamino,N-alkyl-aralkylsulphonylamino, alkoxycarbonylamino,N-alkyl-alkoxycarbonylamino, alkoxycarbonylalkylamino,N-(alkyl)-N-(alkoxycarbonylalkyl)-amino, aralkoxycarbonylamino orN-alkyl-aralkoxycarbonylamino group,

[0209] a (NR₈R₉)CONR₇ group wherein

[0210] R₇ and R₈ in each case denote a hydrogen atom or an alkyl groupand R9 denotes a hydrogen atom or an alkyl, aryl or pyridyl group, whilethe groups R₇, R₈ and R₉ may be identical or different, or

[0211] R₇ and R₈ together denote a n-C₂₋₄-alkylene group and R₉ is ahydrogen atom or an alkyl, aryl or pyridyl group,

[0212] an alkyleneimino group with 5 to 7 cyclic atoms in thealkyleneimino moiety optionally substituted by 1 to 2 alkyl groups,while in the abovementioned 6- to 7-membered alkyleneimino moieties amethylene group in the 4-position of the alkyleneimino moiety may bereplaced in each case by an oxygen or sulphur atom, by a carbonyl,sulphinyl, sulphonyl, imino, N-alkylimino, N-alkylcarbonyl-imino,N-alkylsulphonyl-imino, N-arylimino or N-aralkyl-imino group,

[0213] an (alkyleneimino)carbonyl group with in each case 4 to 7 cyclicatoms in the alkyleneimino moiety optionally substituted by 1 to 2 alkylgroups, while in the abovementioned 6- to 7-membered alkyleneiminomoieties a methylene group in the 4-position may be replaced in eachcase by an oxygen or sulphur atom, by a sulphinyl, sulphonyl, imino,N-alkyl-imino, N-alkylcarbonyl-imino, N-alkylsulphonyl-imino,N-aryl-imino or N-aralkyl-imino group,

[0214] a 4- to 7-membered alkyleneimino group substituted by a hydroxy,alkoxy, amino, alkylamino, dialkylamino, alkylcarbonylamino,N-alkyl-alkylcarbonylamino, alkylsulphonylamino,N-alkyl-alkylsulphonylamino, hydroxyalkyl, carboxy, alkoxycarbonyl,aminocarbonyl, alkylaminocarbonyl or dialkylaminocarbonyl group,

[0215] an alkyl group substituted by a carboxy, alkoxycarbonyl,aminocarbonyl, alkylaminocarbonyl, dialkylaminocarbonyl, cyano, hydroxy,alkoxy, aryloxy, amino, alkylamino, dialkylamino, alkylcarbonylamino,N-alkyl-alkylcarbonylamino, alkoxycarbonylamino,N-alkyl-alkoxycarbonylamino, alkylsulphonylamino,N-alkyl-alkylsulphonylamino, arylcarbonylamino,N-alkyl-arylcarbonylamino, arylsulphonylamino,N-alkyl-arylsulphonylamino, dialkylaminocarbonylalkylamino,N-(alkyl)-N-(dialkylaminocarbonylalkyl)-amino, dialkylaminoalkoxy,alkylsulphenyl, alkylsulphinyl, alkylsulphonyl, arylsulphenyl,arylsulphinyl or arylsulphonyl group,

[0216] an (alkyleneimino)alkyl group with in each case 4 to 7 cyclicatoms in the alkyleneimino moiety optionally substituted by 1 to 2 alkylgroups, while in the abovementioned 6- to 7-membered alkyleneiminomoieties a methylene group in the 4-position may be replaced in eachcase by an oxygen or sulphur atom, by a sulphinyl, sulphonyl, imino,N-alkyl-imino or N-alkylcarbonyl-imino group,

[0217] an (alkyleneimino)carbonylalkyl group with in each case 4 to 7cyclic atoms in the alkyleneimino moiety optionally substituted by 1 to2 alkyl groups, while in the abovementioned 6- to 7-memberedalkyleneimino moieties a methylene group in the 4-position may bereplaced in each case by an oxygen or sulphur atom, by a sulphinyl,sulphonyl, imino or N-alkyl-imino group,

[0218] a (carboxyalkyl)oxy, (alkoxycarbonylalkyl)oxy,(aminocarbonylalkyl)oxy, (alkylaminocarbonylalkyl)oxy or(dialkylaminocarbonylalkyl)oxy group,

[0219] a 3,4-dihydro-1H-quinazolin-2-on-3-yl or1H-benzimidazol-2-on-1-yl group optionally substituted in the arylmoiety by one or two fluorine, chlorine, bromine or iodine atoms or oneor two nitro, alkyl, alkoxy or cyano groups in each case, while thesubstituents may be identical or different, or

[0220] R_(c)NR_(d) denotes a 6- to 7-membered alkyleneimino groupoptionally substituted by 1 to 2 alkyl groups or by an aryl group, whichmay additionally be substituted by the group R₆, while in theabovementioned alkyleneimino groups a methylene group in the 4-positionis replaced in each case by an oxygen or sulphur atom, by a carbonyl,sulphinyl, sulphonyl or R₁₀N group, where

[0221] R₁₀ denotes a hydrogen atom, an alkyl, hydroxy-C₂₋₄-alkyl,amino-C₂₋₄-alkyl, alkylamino-C₂₋₄-alkyl, dialkylamino-C₂₋₄-alkyl,(hydroxy-C₂₋₄-alkoxy)-C₂₋₄-alkyl, aminocarbonylalkyl,alkylaminocarbonylalkyl, dialkylaminocarbonylalkyl, aryl, formyl,alkylcarbonyl, alkylsulphonyl, arylcarbonyl, arylsulphonyl,aralkylcarbonyl, aralkylsulphonyl, alkoxycarbonyl, aralkoxycarbonyl,cyano, aminocarbonyl, alkylaminocarbonyl or dialkylaminocarbonyl group,

[0222] an amino-alkylcarbonyl, alkylamino-alkylcarbonyl,dialkylamino-alkylcarbonyl-group,

[0223] a methyl group substituted by one or two aryl groups, while thearyl moieties may be substituted independently of one another by one ortwo fluorine, chlorine, bromine or iodine atoms or one or two nitro,alkyl, hydroxy or alkoxy groups in each case, while the substituents maybe identical or different,

[0224] a 2-, 3- or 4-pyridyl group,

[0225] a 2-, 4- or 5-pyrimidyl group,

[0226] a phenyl group optionally substituted by one or two fluorine,chlorine, bromine or iodine atoms or one or two nitro, trifluoromethyl,alkyl, hydroxy, alkoxy, amino, alkylamino, dialkylamino, carboxy,alkoxycarbonyl, aminocarbonyl, alkylaminocarbonyl, dialkylaminocarbonylor cyano groups, while the substituents may be identical or different,

[0227] a 8-methyl-8-aza-bicyclo[3.2.1]oct-3-yl group,

[0228] or an (alkyleneimino)carbonyl or (alkyleneimino)carbonylalkylgroup with in each case 5 to 7 cyclic atoms in the alkyleneimino moiety,while in the above-mentioned 6- to 7-membered alkyleneimino moieties amethylene group in the 4-position may be replaced in each case by anoxygen or sulphur atom, by a sulphinyl, sulphonyl, imino, N-alkyl-imino,N-alkylearbonyl-imino or N-aralkyl-imino group, or

[0229] R_(c)NR_(d) denotes a 3-thiazolidinyl group substituted in the4-position by a carboxy, alkoxycarbonyl, aminocarbonyl,alkylaminocarbonyl or dialkylaminocarbonyl group, or

[0230] R_(c)NR_(d) denotes a 1-piperidinyl group optionally substitutedby 1 to 2 alkyl groups, wherein two hydrogen atoms on the carbonskeleton are replaced by a straight-chain alkylene bridge, this bridgecontaining 2 to 6 carbon atoms, if the two hydrogen atoms are located onthe same carbon atom, or 1 to 5 carbon atoms if the two hydrogen atomsare located on adjacent carbon atoms, or 1 to 4 carbon atoms if the twohydrogen atoms are located on carbon atoms which are separated by oneatom, or 1 to 3 carbon atoms if the two hydrogen atoms are located oncarbon atoms which are separated by two atoms, while the abovementioned1-piperidinyl groups are additionally substituted by the group R₆, whichis as hereinbefore defined,

[0231] a 1-pyrrolidinyl or 1-piperidinyl group optionally substituted by1 to 2 alkyl groups, wherein the two hydrogen atoms of a methylene groupare replaced by a straight-chain C3-6-alkylene bridge, while in eachcase a methylene group in the C₃₋₆-alkylene bridge is replaced by a R₁₀Ngroup, where R₁₀ is as hereinbefore defined, while the bicyclic ringthus formed is optionally additionally substituted by a hydroxy, alkoxy,amino, alkylamino, dialkylamino, cyano, alkylcarbonylamino,alkylsulphonylamino, alkoxycarbonylamino, arylcarbonyl, carboxy,alkoxycarbonyl, aminocarbonyl, alkylaminocarbonyl ordialkylaminocarbonyl group,

[0232] a group of the structure

[0233] optionally substituted by 1 or 2 alkyl groups in the alkylenemoieties

[0234] wherein

[0235] p and q, which may be identical or different, independently ofone another denote the number 1 or 2, and

[0236] the unit —V=W—X═Y— denotes one of the groups (a) or (b):

[0237] —N═C—C═C— (a),

[0238] —C═N—C═C— (b),

[0239] while one of the available carbon atoms of the groups (a) or (b)may be substituted by a hydroxy, alkoxy, amino, alkylamino ordialkylamino group and the remaining available carbon atoms of thegroups (a) or (b) are substituted by a hydrogen atom, an alkyl or arylgroup, or

[0240] —V═W— taken together represent an oxygen or sulphur atom or animino, N-alkyl-imino or N-aryl-imino group and —X═Y— represents one ofthe groups —N═C or —C—N—, or,

[0241] if n and m are not the same,

[0242] —X═Y— taken together represent an oxygen or sulphur atom or animino, N-alkyl-imino or N-aryl-imino group and —V═W— represents one ofthe groups —N═C or —C═N—, or

[0243] R_(c) represents a hydrogen atom, an aralkyl or a C₁₋₆-alkylgroup,

[0244] an alkyl group which is substituted

[0245] by a hydroxy, alkoxy, aryloxy, aralkoxy, amino, alkylamino,dialkylamino, alkylcarbonylamino, N-alkyl-alkylcarbonylamino,alkylsulphonylamino, N-alkyl-alkylsulphonylamino,trifluoromethylsulphonylamino, N-alkyl-trifluoromethylsulphonylamino,carboxy, alkoxycarbonyl, aminocarbonyl, alkylaminocarbonyl,dialkylaminocarbonyl, cyano or by a 2-, 3- or 4-pyridyl group with theproviso that the hetero atoms are separated from the nitrogen atom ofthe R_(c)NR_(d) group by two or more carbon atoms,

[0246] a C₃₋₅-alkenyl group, while the vinyl moiety may not be attachedto the nitrogen atom of the R_(c)NR_(d) group,

[0247] a C₃₋₅-alkynyl group, while the ethynyl moiety may not beattached to the nitrogen atom of the R_(c)NR_(d) group, and

[0248] R_(d) denotes a C₁₋₁₀-alkyl group which is substituted by a groupselected from the groups (a) to (n):

[0249] (a) a carboxy, alkoxycarbonyl, aminocarbonyl, alkylaminocarbonyl,dialkylaminocarbonyl, cyano, hydroxy, alkoxy, aryloxy, aralkoxy,alkylcarbonylamino, amino, alkylamino, dialkylamino, naphthylamino,aralkylamino, diaralkylamino or N-alkyl-aralkylamino group,

[0250] (b) a phenylamino or pyridylamino group optionally substituted inthe aryl moiety by a fluorine, chlorine, bromine or iodine atom or anitro, trifluoromethyl, alkyl, hydroxy, alkoxy, amino, alkylamino,dialkylamino, carboxy, alkoxycarbonyl, aminocarbonyl,alkylaminocarbonyl, dialkylaminocarbonyl or cyano group,

[0251] (c) a methoxy group substituted by one, two or three aryl groups,

[0252] (d) a carboxyalkylaminocarbonyl,alkoxycarbonylalkylaminocarbonyl, aminocarbonylalkylaminocarbonyl,alkylaminocarbonylalkylaminocarbonyl,dialkylaminocarbonylalkylaminocarbonyl, arylaminocarbonyl,N-alkylarylaminocarbonyl, aralkylaminocarbonyl,N-alkyl-aralkylaminocarbonyl,

[0253] (e) a group of formula-C(═NH)NH₂,

[0254] (f) an (alkyleneimino)carbonyl group with in each case 5 to 7cyclic atoms in the alkyleneimino moiety optionally substituted by 1 to2 alkyl groups, while in the abovementioned 6- to 7-memberedalkyleneimino groups a methylene group in the 4-position may be replacedin each case by an oxygen or sulphur atom, by a sulphinyl, sulphonyl,imino, N-alkyl-imino, N-alkylcarbonyl-imino, N-alkylsulphonyl-imino,N-aryl-imino or N-aralkyl-imino group,

[0255] (g) a 4- to 7-membered alkyleneimino group optionally substitutedby 1 to 2 alkyl groups, while in the abovementioned 6- to 7-memberedalkyleneimino groups a methylene group in the 4-position may be replacedin each case by an oxygen or sulphur atom, by a sulphinyl, sulphonyl orR₁₀N group, where R₁₀ is as hereinbefore defined, and additionally inthe abovementioned 5- to 7-membered alkyleneimino groups a methylenegroup adjacent to the nitrogen atoms may be replaced by a carbonyl groupin each case,

[0256] (h) a 5- to 7-membered alkyleneimino group optionally substitutedby 1 to 2 alkyl groups which is substituted by a hydroxyalkyl,aminoalkyl, alkylaminoalkyl or dialkylaminoalkyl group,

[0257] (i) an alkylsulphonylamino, N-alkyl-alkylsulphonylamino,arylcarbonylamino, N-alkyl-arylcarbonylamino, alkylcarbonylamino,N-alkyl-alkylcarbonylamino, alkoxy-alkylcarbonylamino,dialkylamino-alkylcarbonylamino, arylsulphonylamino,N-alkyl-arylsulphonylamino, aralkylcarbonylamino,N-alkylaralkylcarbonylamino, aralkylsulphonylamino,N-alkyl-aralkylsulphonylamino, alkoxycarbonylamino,N-alkyl-alkoxycarbonylamino, aralkoxycarbonylamino orN-alkyl-aralkoxycarbonylamino group, a (R₉NR₈)—CO—NR₇ group, where R₇,R₈ and R₉ are as hereinbefore defined,

[0258] (k) a 2-aza-bicyclo[2.2.1]hept-5-en-2-yl group,

[0259] (l) an alkylsulphenyl, alkylsulphinyl, alkylsulphonyl,arylsulphenyl, arylsulphinyl or arylsulphonyl group,

[0260] (m) a C₄₋₇-cycloalkyl group substituted by R₆ and optionallyadditionally substituted by 1 to 2 alkyl groups, while R₆ is ashereinbefore defined,

[0261] (n) a C₅₋₇-cycloalkyl group optionally substituted by 1 to 4alkyl groups wherein a methylene group is replaced by an oxygen atom ora NR₁₀ group, while R₁₀ is as hereinbefore defined,

[0262] a 4-piperidinyl-methyl group which is substituted in the1-position by R₁₀ and additionally in the 4-position by a hydroxy group,where R₁₀ is as hereinbefore defined, and wherein additionally ahydrogen atom in each of positions 2 and 6 of the piperidinyl structureare together replaced by a C₂₋₃-alkylene bridge,

[0263] a methyl group substituted by a3-hydroxy-1,3-dihydro-indol-2-on-3-yl or2-aminocarbonyl-1,3-dihydro-isoindol-5-yl group,

[0264] a group of the structure

[0265] substituted in the aryl moiety by a carboxy or carboxyalkyl groupand optionally additionally substituted in the alkylene moiety by 1 or 2alkyl groups

[0266] while p and q, which may be identical or different, denote thenumber 0, 1 or 2, but p and q together must at least yield the number 2,

[0267] a C₃₋₆-alkyl group substituted by a hydroxy group andadditionally substituted by an amino, alkylamino, dialkylamino, hydroxy,alkoxy, 1-pyrrolidinyl, 1-piperidinyl or morpholino group,

[0268] a C₂₋₆-alkyl group substituted by a carboxy group andadditionally substituted by an amino, hydroxy, aminocarbonyl orbenzyloxycarbonylamino group,

[0269] a C₂₋₄-alkyl group which is substituted by a C₂₋₄-alkylsulphenylgroup, which is substituted in the ω-position by a ω-amino group,

[0270] a C₂₋₄-alkyl group which is substituted by a C₂₋₄-alkoxy group,which is substituted in the ω-position by an amino, hydroxy or alkoxygroup,

[0271] a C₂₋₄-alkyl group which is substituted by aC₂₋₄-alkoxy-C₂₋₄-alkoxy group, which is substituted in the ω-position byan amino or hydroxy group,

[0272] a C₄₋₇-cycloalkyl group optionally substituted by 1 to 2 alkylgroups, which is additionally substituted by R₆, which is ashereinbefore defined,

[0273] a C₄₋₇-cycloalkyl group optionally substituted by 1 to 2 alkylgroups, which may additionally be substituted by R₆, while in thecycloalkyl moiety a methylene group is replaced by an oxygen or sulphuratom, by a sulphinyl, sulphonyl or R₁₀N group, while R₆ and R₁₀ are ashereinbefore defined,

[0274] a methyl group substituted by a3-hydroxy-1,3-dihydro-indol-2-on-3-yl or2-aminocarbonyl-1,3-dihydro-isoindol-5-yl group,

[0275] a C₁₋₆-alkyl group substituted by an aryl group, while theabovementioned aryl moiety is substituted by an alkoxycarbonyl, carboxy,carboxyalkyl, aminosulphonyl, trifluoromethoxy, cyano, aminoalkyl,amino, alkylamino, dialkylamino, nitro, 2H-pyridazin-3-on-6-yl,hydroxyphenyl, hydroxyalkyl, hydroxy or alkoxy group,

[0276] an aralkyl group which is substituted in the aryl moiety by analkoxy or hydroxy group and additionally by an alkoxycarbonyl, carboxy,alkoxy or hydroxy group,

[0277] a C₁₋₆-alkyl group substituted by a 2-pyridyl, 3-pyridyl,4-pyridyl, 2-pyrazinyl-, 1H-pyrrol-2-yl, 1H-pyrazol-4-yl-,1H-pyrazol-5-yl, 1H-imidazol-1-yl, 1H-imidazol-4-yl, 1H-indol-3-yl or1H-benzimidazol-2-yl group, while the abovementioned heteroaryl moietiesat the available carbon atoms may additionally be substituted in eachcase by one or two groups selected from fluorine, chlorine, bromine oriodine atoms, alkyl, alkoxycarbonyl, carboxy, trifluoromethyl,trifluoromethoxy, cyano, amino, alkylamino, dialkylamino, nitro, hydroxyor alkoxy groups, while the substituents may be identical or different,a C₁₋₆-alkyl group substituted by a carboxy, alkoxycarbonyl,aminocarbonyl, alkylaminocarbonyl, dialkylaminocarbonyl,aralkylaminocarbonyl, cyano, hydroxy, alkoxy, aryloxy, amino,alkylamino, dialkylamino, alkylcarbonylamino or alkoxycarbonylaminogroup, which is additionally substituted by one or two aryl groups or aheteroaryl group, while the heteroaryl group denotes a 2-pyridyl,3-pyridyl, 4-pyridyl, 2-pyrazinyl-, 1H-pyrrol-2-yl, 1H-pyrazol-4-yl-,1H-pyrazol-5-yl, 1H-imidazol-1-yl, 1H-imidazol-4-yl, 1H-indol-3-yl or1H-benzimidazol-2-yl group, while the above-mentioned aryl or heteroarylmoieties at the available carbon atoms may additionally be substitutedin each case by one or two groups selected from fluorine, chlorine,bromine or iodine atoms, alkyl, alkoxycarbonyl, carboxy,trifluoromethyl, trifluoromethoxy, cyano, amino, alkylamino,dialkylamino, nitro, hydroxy or alkoxy groups, while the substituentsmay be identical or different,

[0278] a C₁₋₆-alkyl group substituted by an aryl group which issubstituted in the aryl moiety by a hydroxy or amino group and isadditionally substituted by two fluorine, chlorine, bromine or iodineatoms, while the substituents may be identical or different,

[0279] a C₂₋₆-alkyl group substituted by a carboxy or alkoxycarbonylgroup which is additionally substituted by an amino, alkylamino,dialkylamino, alkylcarbonylamino, arylcarbonylamino, arylsulphonylamino,alkoxycarbonylamino or aralkoxycarbonylamino group,

[0280] a 3-quinuclidinyl or 4-quinuclidinyl group, and

[0281] R_(e) denotes a fluorine, chlorine, bromine or iodine atom,

[0282] an alkyl, alkoxy, dialkylamino, allyl, ethynyl, methylsulphenyl,methylsulphonyl, alkoxymethyl, nitro, cyano or dialkylaminomethyl group,

[0283] a methyl, ethyl, methylsulphenyl or methoxy group substituted by1 to 3 fluorine atoms,

[0284] an alkyleneimino or alkyleneimino-methyl group with 4 to 7 cyclicatoms in the alkyleneimino moiety in each case, while in a 6 or7-membered alkyleneimino moiety a methylene group in the 4-position maybe replaced in each case by an oxygen or sulphur atom, by anN-alkyl-imino, N-alkylcarbonyl-imino, N-alkylsulphonyl-imino,N-aryl-imino or N-aralkyl-imino group,

[0285] while, unless otherwise specified, the abovementioned alkyl,alkylene and alkoxy moieties in each case contain 1 to 4 carbon atoms,

[0286] optionally in the form of the tautomers, racemates, enantiomers,diastereomers and mixtures thereof, and optionally also thepharmacologically acceptable acid addition salts thereof,

[0287] while, unless otherwise stated, each carbon atom in theabovementioned alkyl, alkylene or cycloalkylene moieties which is boundto a nitrogen, oxygen or sulphur atom, cannot be bound to any otherhalogen, nitrogen, oxygen or sulphur atom.

[0288] Particularly preferred compounds of formula I are those wherein

[0289] R_(a) denotes a hydrogen atom or a methyl group,

[0290] R_(b) denotes a naphthyl group optionally substituted by afluorine, chlorine or bromine atom or by a carboxy, C₁₋₂ alkyl, C₁₋₂alkoxy, cyano or trifluoromethyl group,

[0291] a benzyl or 2-phenethyl group optionally substituted in the arylmoiety by a hydroxy, cyano, trifluoromethyl, nitro, carboxy,alkoxycarbonyl, aminocarbonyl, alkylaminocarbonyl, dialkylaminocarbonyl,amino, alkylamino or dialkylamino group or one or two fluorine, chlorineor bromine atoms or one or two alkyl or alkoxy groups, while thesubstituents may be identical or different, and while the alkylenemoiety of the abovementioned aralkyl groups may be substituted by one ortwo methyl groups, or

[0292] a 5- or 6-indazolyl or 1,3-dihydro-2-oxo-indol-6-yl group or

[0293] a phenyl group optionally substituted by the groups R₁ to R₃,where

[0294] R₁ denotes a fluorine, chlorine, bromine or iodine atom, a C₁₋₂alkyl, trifluoromethyl, aminocarbonyl, carboxy, alkoxycarbonyl, cyano,phenylaminocarbonyl, benzylaminocarbonyl, aminosulphonyl,methylaminosulphonyl, dimethylaminosulphonyl, morpholinosulphonyl,N-methylpiperazinosulphonyl, homopiperazinosulphonyl,2,6-dimethylpiperazin-4-yl, 2-aminopyridyl-N-sulphonyl, morpholino,4-methyl-1-piperazinyl, (N-methyl-N-methylsulphonyl)amino,2-carboxy-1-ethyl, dimethylamino-1-ethyl or nitro group,

[0295] a methyl group which is substituted by a1,2,4,5-tetrahydro-benzo[d]azepin-3-yl, a dialkylamino or a pyrrolidino,piperidino, 2,6-dimethyl-piperidino-1-yl, 4-methoxy-piperidino-1-yl,morpholino, S-dioxo-thiomorpholino, piperazino or 4-methyl-1-piperazinylgroup, a fluoroalkylamino group of formula

—(CH₂)_(r)—(CF₂)_(s)-Q,

[0296]  wherein

[0297] r denotes 0 or an integer from 1 to 3,

[0298] s denotes an integer from 1 to 3, and

[0299] Q denotes hydrogen, fluorine or chlorine,

[0300] R₂ denotes a fluorine or chlorine atom, a hydroxy, amino ormethyl group and

[0301] R₃ denotes a chlorine atom, or

[0302] a tetrazolyl, triazolyl, imidazolyl or pyrazolyl group,

[0303] wherein the point of attachment is a carbon atom or a nitrogenatom and on the ring a hydrogen atom may be replaced by an alkyl group,or

[0304] an aminosulphonyl, methylaminosulphonyl, dimethylaminosulphonyl,morpholinosulphonyl, N-methylpiperazinosulphonyl,homopiperazinosulphonyl or 2-aminopyridyl-N-sulphonyl group,

[0305] R₂ and R₃ taken together represent a group of the formula

—(CH₂)_(m)—NR₅—(CH₂)_(n)

[0306]  wherein n and m independently of each other denote 1 or 2, and

[0307]  R₅ denotes a fluoroalkyl group of formula

—(CH₂)_(r′)—(CF₂)_(s′)-Q′,

[0308] wherein

[0309] r′ denotes 0 or an integer from 1 to 3,

[0310] s′ denotes an integer from 1 to 3, and

[0311] Q′ denotes hydrogen, fluorne or chlorine,

[0312] the group R_(c)NR_(d)

[0313] denotes a 5- to 7-membered alkyleneimino group substituted by thegroup R₆,

[0314] while R₆ denotes a hydroxy, alkoxy, aryloxy, amino, alkylamino,dialkylamino, alkylcarbonylamino, N-alkyl-alkylcarbonylamino,alkoxycarbonylalkylamino, N-(alkyl)-N-(alkoxycarbonylalkyl)-amino,alkylsulphenyl, alkylsulphinyl, alkylsulphonyl, arylsulphenyl,arylsulphinyl, arylsulphonyl, carboxy, alkoxycarbonyl, aminocarbonyl,alkylaminocarbonyl, dialkylaminocarbonyl or cyano group,

[0315] an alkyl group which is substituted by a hydroxy, amino,alkylamino, dialkylamino, alkylcarbonylamino,N-alkyl-alkylcarbonylamino, dialkylaminocarbonylalkylamino,N-(alkyl)-N-(dialkylaminocarbonylalkyl)-amino, alkoxycarbonyl, carboxyor dialkylaminoalkoxy group or by a 5- to 7-membered alkyleneiminogroup, while in the abovementioned 6- to 7-membered alkyleneimino groupsa methylene group in the 4-position may be replaced by an oxygen orsulphur atom or by an imino, N-alkyl-imino or N-alkylcarbonyl-iminogroup,

[0316] an alkyleneimino group with 5 to 7 cyclic atoms in thealkyleneimino moiety, while in the abovementioned 6- to 7-memberedalkyleneimino moieties a methylene group in the 4-position may bereplaced in each case by an oxygen or sulphur atom, by an N-alkyl-imino,N-alkylcarbonyl-imino or N-aralkyl-imino group,

[0317] an alkyleneimino group with 5 to 7 cyclic atoms in thealkyleneimino moiety substituted by a hydroxy, amino, alkylamino,dialkylamino, carboxy, alkoxycarbonyl, aminocarbonyl, alkylaminocarbonylor dialkylaminocarbonyl group,

[0318] a 3,4-dihydro-1H-quinazolin-2-on-3-yl or a1H-benzimidazol-2-on-1-yl group optionally substituted in the arylmoiety by a fluorine, chlorine or bromine atom or a nitro, alkyl, alkoxyor cyano group in each case,

[0319] a 6- to 7-membered alkyleneimino group optionally substituted by1 or 2 alkyl groups, while a methylene group in the 4-position isreplaced by an oxygen or sulphur atom, by a sulphinyl, sulphonyl or anNR₁₀ group,

[0320] where R₁₀ denotes a hydrogen atom or an alkyl, aralkyl,amino-C₂₋₄-alkyl, hydroxy-C₂₋₄-alkyl, alkylcarbonyl, aralkoxycarbonyl,alkylsulphonyl, arylcarbonyl, arylsulphonyl,

[0321] an (alkyleneimino)carbonylalkyl group with 5 to 7 cyclic atoms inthe alkyleneimino moiety, while in the abovementioned 6- to 7-memberedalkyleneimino moieties a methylene group in the 4-position may bereplaced in each case by an oxygen or sulphur atom, by an N-alkyl-imino,N-alkylcarbonyl-imino or N-aralkyl-imino group,

[0322] a 2-, 3- or 4-pyridyl group,

[0323] a 2-, 3- or 4-pyrimidyl group,

[0324] a phenyl group optionally substituted by one or two fluorine,chlorine, bromine or iodine atoms or one or two nitro, alkyl, hydroxy,alkoxy, amino, alkylamino, dialkylamino, carboxy, alkoxycarbonyl,aminocarbonyl, alkylaminocarbonyl, dialkylaminocarbonyl or cyano groups,while the substituents may be identical or different,

[0325] an 8-methyl-8-aza-bicyclo[3.2.1] oct-3-yl group,

[0326] a benzhydryl group, wherein independently of one another eachphenyl moiety may be substituted by a fluorine, chlorine, bromine oriodine atom or a nitro, alkyl, hydroxy, alkoxy group, while thesubstituents may be identical or different,

[0327] a 6- or 7-membered alkyleneimino group substituted by a phenylgroup, which is additionally substituted by a hydroxy, carboxy,alkoxycarbonyl or cyano group or wherein a methylene group in the4-position is replaced by a carbonyl group,

[0328] a 3-thiazolidinyl group substituted in the 4-position by acarboxy, alkoxycarbonyl, aminocarbonyl, alkylaminocarbonyl ordialkylaminocarbonyl group,

[0329] a group of the structure

[0330] wherein p and q, which may be identical or different,independently of one another represent the number 1 or 2, while theimidazo ring may be substituted by one or two alkyl or aryl groups,while the substituents may be identical or different,

[0331] a 1-pyrrolidinyl or 1-piperidinyl group, wherein the two hydrogenatoms of a methylene group are replaced by a straight-chainC₃₋₅-alkylene bridge, while in each case a methylene group in theC₃₋₅-alkylene bridge is replaced by an imino, N-alkyl-imino orN-(aralkyl)imino group, while the bicyclic ring thus formed isoptionally additionally substituted by a hydroxy group,

[0332] a 1-piperidinyl group which is substituted in the 4-position by ahydroxy, alkoxy or aralkoxy group and wherein additionally one of thehydrogen atoms in each of positions 2 and 6 of the piperidinyl structureare together replaced by an ethylene bridge, or

[0333] R_(c) denotes a hydrogen atom or a C₁₋₆-alkyl group,

[0334] an alkyl group substituted by a phenyl or a 2-, 3- or 4-pyridylgroup,

[0335] a C₂₋₄-alkyl group substituted by a hydroxy or alkoxy group, and

[0336] R_(d) represents a C₁₋₆-alkyl group which is substituted by agroup selected from the groups (a) to (j):

[0337] (a) a group of formula-C(═NH)NH₂,

[0338] (b) a carboxy, alkoxycarbonyl, carboxymethylaminocarbonyl,aminocarbonyl, alkylaminocarbonyl, alkylcarbonylamino,dialkylaminocarbonyl, arylaminocarbonyl, N-alkyl-arylaminocarbonyl,aralkylaminocarbonyl, N-alkyl-aralkylaminocarbonyl or cyano group,

[0339] (c) a hydroxy, amino, alkoxy, alkylamino, dialkylamino,alkylcarbonylamino, N-alkyl-alkylcarbonylamino, alkoxycarbonylamino,alkoxyacetylamino, dialkylaminoacetylamino, N-alkyl-alkoxycarbonylamino,alkylsulphonylamino, N-alkyl-alkylsulphonylamino, arylamino,naphthylamino, aralkylamino, diaralkylamino, N-alkyl-aralkylamino oralkylsulphenyl group,

[0340] (d) a nitro-2-pyridyl-amino group,

[0341] (e) a methoxy group substituted by one, two or three aryl groups,

[0342] (f) a 4- to 7-membered alkyleneimino group, while in theabovementioned 6- to 7-membered alkyleneimino groups a methylene groupin the 4-position may be replaced in each case by an oxygen or sulphuratom, by an imino, N-alkyl-imino, N-(hydroxy-C₂₋₄-alkyl)-imino orN-(amino-C₂₋₄-alkyl)-imino group, and additionally in the abovementioned5- to 7-membered alkyleneimino groups a methylene group adjacent to thenitrogen atoms may be replaced in each case by a carbonyl group,

[0343] (g) a 1-piperidinyl group substituted by a dialkylaminoalkylgroup,

[0344] (h) a 2-aza-bicyclo[2.2.1]hept-5-en-2-yl group,

[0345] (i) a 5- to 7-membered (alkyleneimino)carbonyl group, while inthe abovementioned 6-to 7-membered alkyleneimino groups a methylenegroup in the 4-position may be replaced by an oxygen or sulphur atom orby an imino or N-alkyl-imino group, and

[0346] (j) a (R₈R₉)CONR₇ group wherein

[0347] R₇, R₈ and R₉, which may be identical or different, in each casedenote a hydrogen atom or a methyl group or

[0348] R₇ and R₈ together denote a n-C₂₋₃-alkylene group and R₉ denotesa hydrogen atom or a methyl or 4-pyridyl group or

[0349] R₇ and R₈ denote a hydrogen atom and R9 denotes a phenyl group,

[0350] a cyclohexyl group substituted in the 2-, 3- or 4-position by ahydroxy, amino, alkylamino, dialkylamino, aminomethyl, hydroxymethyl,alkoxycarbonyl, aminocarbonyl, alkylaminocarbonyl, dialkylaminocarbonylor carboxy group,

[0351] a cyclohexyl group substituted in the 4-position by acarboxyalkyl group,

[0352] an ethyl group substituted in the 2-position by a2-amino-1-ethylthio, 2-hydroxy-1-ethoxy, 2-(2-amino-1-ethoxy)-1-ethoxyor 2-(2-hydroxy-1-ethoxy)-1-ethoxy group,

[0353] a propyl group substituted in the 3-position by a3-amino-1-propoxy or 2-(3-amino-1-propoxy)-1-ethoxy group,

[0354] a C₁₋₂-alkyl group substituted by a C₅₋₆-cycloalkyl group, whilethe cycloalkyl moiety is substituted by a hydroxy, aminomethyl,dimethylaminomethyl, 2-carboxyethyl or tert.-butyloxycarbonylaminomethylgroup or wherein in the cycloalkyl moiety a methylene group is replacedby an oxygen atom, an N-alkyl-imino or N-(2-dialkylaminoacetyl)iminogroup,

[0355] a 4-piperidinyl-methyl group which is substituted in the1-position by an alkyl or aralkyl group and additionally in the4-position by a hydroxy group and wherein additionally in each case ahydrogen atom in each of positions 2 and 6 of the piperidinyl structureare together replaced by an ethylene bridge,

[0356] a 3-pyrrolidinyl or a 3- or 4-piperidinyl group which issubstituted in each case in the 1-position by an alkyl, aralkyl orarylsulphonyl group,

[0357] a 4-piperidinyl group which is substituted in the 1-position byan alkyl, aralkyl or aryl group and is additionally substituted in the4-position by a carboxy group,

[0358] an aralkyl group which is substituted in the aryl moiety by ahydroxy, aminosulphonyl, carboxy, nitro, amino, aminomethyl,2-amino-1-ethyl, alkoxycarbonyl, 4-hydroxyphenyl or2H-pyridazin-3-on-6-yl group,

[0359] a methyl group substituted by a3-hydroxy-1,3-dihydro-indol-2-on-3-yl or2-aminocarbonyl-1,3-dihydro-isoindol-5-yl group,

[0360] a 2-indanyl group substituted in the aryl moiety by a3-carboxy-1-propyl group,

[0361] an alkyl group substituted by a 1H-2-benzimidazolyl or4-amino-3,5-dichlorophenyl group,

[0362] an aralkyl group which is substituted in the alkyl moiety by ahydroxy, amino, alkylamino, dialkylamino, aminocarbonyl,alkylaminocarbonyl, dialkylaminocarbonyl, aralkylaminocarbonyl, carboxyor cyano group and is optionally additionally substituted in the arylmoiety by one or two fluorine, chlorine or bromine atoms or one or twohydroxy or alkoxy groups, while the substituents may be identical ordifferent,

[0363] an alkyl group substituted by a carboxy group and additionally bytwo phenyl groups,

[0364] a C₂₋₆-alkyl group substituted by a carboxy group andadditionally substituted by a hydroxy, aminocarbonyl, 1H-imidazol-4-ylor benzyloxycarbonylamino group,

[0365] an alkyl group substituted by an alkoxycarbonyl group andadditionally by a pyridyl group,

[0366] a C₃₋₆-alkyl group substituted by a hydroxy group andadditionally by an amino, alkylamino, dialkylamino, hydroxy, alkoxy,1-pyrrolidinyl, 1-piperidinyl or morpholino group,

[0367] an aralkyl group which is substituted in the aryl moiety by analkoxy and additionally by a carboxy or hydroxy group,

[0368] an alkyl group substituted by a 2-pyridyl, 3-pyridyl, 4-pyridyl,2-pyrazinyl, 3-chloro-5-trifluoromethyl-2-pyridyl,1-methyl-1H-pyrrol-2-yl, 1H-pyrazol-4-yl,4-ethoxycarbonyl-1H-pyrazol-5-yl, 1H-imidazol-1-yl, 1H-imidazol-4-yl,1H-indol-3-yl or 6-methoxy-1H-benzimidazol-2-yl group,

[0369] a 1-pentyl group substituted in the 5-position by analkoxycarbonyl group, which is additionally substituted in the 5position by an amino, alkylcarbonylamino, arylcarbonylamino,arylsulphonylamino, alkoxycarbonylamino or aralkoxycarbonylamino group,

[0370] R_(e) denotes a fluorine, chlorine bromine or iodine atom,

[0371] an alkyl, alkoxy, dimethylamino, allyl, ethynyl, trifluoromethyl,methyldifluoromethylene, methylsulphenyl, trifluoromethylsulphenyl,methylsulphonyl, methoxymethyl, nitro, cyano or dimethylaminomethylgroup,

[0372] while, unless otherwise specified, the abovementioned alkyl,alkylene and alkoxy moieties each contain 1 to 4 carbon atoms,

[0373] optionally in the form of the tautomers, racemates, enantiomers,diastereomers and mixtures thereof, and optionally also thepharmacologically acceptable acid addition salts thereof,

[0374] while, unless otherwise stated, each carbon atom in theabovementioned alkyl, alkylene or cycloalkylene moieties which is boundto a nitrogen, oxygen or sulphur atom cannot be bound to any otherhalogen, nitrogen, oxygen or sulphur atom.

[0375] Most particularly preferred compounds of formula I are thosewherein

[0376] R_(a) denotes a hydrogen atom,

[0377] R_(b) denotes a 1-naphthyl group or a 2-naphthyl group optionallysubstituted in the 5 position by a carboxy group,

[0378] a benzyl group optionally substituted in the 2 position of thephenyl moiety by a chlorine or bromine atom,

[0379] a 1,3-dihydro-2-oxo-indol-6-yl, benzotriazol-5-yl,benzimidazol-5-yl, indazol-5-yl or indazol-6-yl group,

[0380] a phenyl group optionally substituted in the 4 position of thephenyl moiety by a fluorine, chlorine or bromine atom, by a cyano,aminosulphonyl, methylaminosulphonyl, dimethylaminosulphonyl,morpholinosulphonyl, N-methylpiperazinosulphonyl,homopiperazinosulphonyl, 2,6-dimethylpiperazin-4-yl,2-aminopyridyl-N-sulphonyl, carboxy, piperidinomethyl,1,2,4,5-tetrahydro-benzo[d]azepin-3-yl-methyl, 2-carboxy-1-ethyl,phenylaminocarbonyl, benzylaminocarbonyl, aminocarbonyl,methoxycarbonyl, (N-methyl-N-methylsulphonyl)amino, diethylaminomethyl,3-diethylamino-1-propyloxy, morpholino, 4-methyl-1-piperazinyl,2-H-tetrazol-5-yl, 1-H-imidazol-4-yl or nitro group,

[0381] a phenyl group substituted in the 3 position of the phenyl moietyby a chlorine or bromine atom, by a cyano, aminocarbonyl, carboxy,ethoxycarbonyl or nitro group or by a group of formula

—CH₂—NH—(CH₂)_(r)—C_(s)F_(2s+1),

[0382] wherein r denotes 1 or 2 and s denotes 1, 2 or 3,

[0383] a 3,4-dichlorophenyl, 3,5-dichlorophenyl,4-amino-3,5-dichlorophenyl, 3-chloro-4-fluorophenyl,4-chloro-3-methylphenyl, 4-chloro-3-trifluoromethylphenyl,4-bromo-3-chlorophenyl or 3-hydroxy-4-methylphenyl group, or

[0384] a group of formula

[0385] wherein r denotes 1 or 2 and s denotes 1, 2 or 3,

[0386] the group R_(c)NR_(d) denotes

[0387] a 1-pyrrolidinyl group substituted in the 2 position by ahydroxymethyl,

[0388] 1-pyrrolidinylmethyl or 2-ethoxycarbonyl-1-ethyl group,

[0389] a 1-pyrrolidinyl group substituted in the 3 position by an amino,acetylamino, N-methyl-acetylamino or tert.butyloxycarbonylamino,

[0390] a 4-carboxy-3-thiazolidinyl, a7-methyl-2,7-diaza-spiro[4.4]non-2-yl or a5-hydroxy-2-methyl-2,8-diaza-spiro[5.5]undec-8-yl group,

[0391] a morpholino or S-oxido-thiomorpholino group

[0392] a 1-piperidinyl group substituted in the 2 position by aethoxycarbonyl, hydroxymethyl, 3-hydroxypropyl, 3-diethylamino-1-propylor 2-(2-diethylaminoethoxy)-1-ethyl group,

[0393] a 1-piperidinyl group substituted in the 3 position by a hydroxy,hydroxymethyl, 3-diethylamino-1-propyl, aminocarbonyl,dimethylaminocarbonyl, carboxy,

[0394] 1-pyrrolidinylmethyl, 4-(1-pyrrolidinyl)-1-butyl,methoxycarbonylmethyl or acetylaminomethyl group,

[0395] a 1-piperidinyl group substituted in the 4-position by anethoxycarbonyl, 3-hydroxypropyl, hydroxy, aminomethyl,2-(2-diethylaminoethoxy)-1-ethyl, 2-carboxy-1-ethyl,N-(2-methoxycarbonyl-1-ethyl)-N-methyl-amino,2-(N-(dimethylaminocarbonylmethyl)-N-methyl-amino)-1-ethyl,N-acetyl-N-methyl-aminomethyl,8-methoxy-3,4-dihydro-1H-quinazolin-2-on-3-yl, 1-piperidinyl,3-hydroxy-1-piperidinyl or 4-ethoxycarbonyl-1-piperidinyl group,

[0396] a 3,5-dimethyl-1-piperazinyl,1,4,6,7-tetrahydro-imidazo[4,5-c]pyridin-5-yl,2-methyl-1,4,6,7-tetrahydro-imidazo[4,5-c]pyridin-5-yl,1,4,5,6,7,8-hexahydro-imidazo[4,5-d]azepin-6-yl,2-methyl-1,4,5,6,7,8-hexahydro-imidazo[4,5-d]azepin-6-yl,3-phenyl-azepan-4-on-1-yl or 4-carboxy-4-phenyl-1-piperidinyl group,

[0397] a 1-piperazinyl group which is optionally substituted in the4-position by a methyl, acetyl, benzyloxycarbonyl, 2-pyridyl,2-pyrimidinyl, 2-nitrophenyl, 3-methoxyphenyl, 4-cyanophenyl,3,4-dimethoxyphenyl, 4-[bis-(4-methoxy-phenyl)]-methyl,8-methyl-8-aza-bicyclo[3.2.1]oct-3-yl, morpholinocarbonylmethyl,2-amino-1-ethyl or 3-hydroxy-1-propyl group,

[0398] a 1-homopiperazinyl group which is optionally substituted in the4-position by a methyl group,

[0399] a 3-hydroxy-8-aza-bicyclo[3.2.1]oct-8-yl group, or

[0400] R_(c) denotes a hydrogen atom or a methyl, ethyl, 2-methoxyethyl,2-hydroxyethyl, i-propyl, n-propyl, n-butyl, benzyl or 3-pyridylmethylgroup, and

[0401] R_(d) denotes a methyl group substituted by a group offormula-C(═NH)NH₂ or a cyano, carboxyl, ethoxycarbonyl, aminocarbonyl,carboxymethylaminocarbonyl, 1-hydroxy-1-cyclohexyl,aminomethylcyclohexyl, 3-hydroxy-8-methyl-8-aza-bicyclo[3.2.1]oct-3-yl,3-hydroxy-1,3-dihydro-indol-2-on-3-yl,2-aminocarbonyl-1,3-dihydro-isoindol-5-yl, 2-tetrahydrofuryl,1-ethyl-2-pyrrolidinyl, 1H-imidazol-4-yl, 1-methyl-4-piperidinyl,1-(2-dimethylaminoacetyl)-4-piperidinyl, 2-pyridyl, 3-pyridyl,4-pyridyl, 2-pyrazinyl, 3-chloro-5-trifluoromethyl-2-pyridyl,4-ethoxycarbonyl-1H-pyrazol-5-yl, 2-carboxyphenyl, 3-carboxyphenyl,2-hydroxyphenyl, 4-hydroxyphenyl, 2-nitrophenyl, 3-nitrophenyl,4-nitrophenyl, 3-aminophenyl, 4-aminophenyl, 4-(aminosulphonyl)phenyl,4′-hydroxybiphenyl, 4-(aminomethyl)phenyl or 4-hydroxy-3-methoxyphenylgroup,

[0402] a C₂₋₅-alkyl group substituted by a carboxy group,

[0403] a C₂₋₅-alkyl group substituted by a hydroxy, acetylamino, aminoor dimethylamino group, with the proviso that the hetero atoms of theabovementioned substituents are separated from the nitrogen atom of theRcNRd group by at least two carbon atoms,

[0404] a benzyl group substituted in the methylene moiety by a carboxyor cyano group,

[0405] a methyl group substituted by a carboxy group and a4-hydroxyphenyl group,

[0406] an ethyl group substituted in the 1-position by a methoxycarbonylor a 1H-benzimidazol-2-yl group,

[0407] an ethyl group substituted in the 2 position by a methoxy,diphenylmethoxy, methylthio, methylamino, diethylamino,diisopropylamino, acetylamino, N-methylacetylamino,2-methoxyacetylamino, 2-dimethylaminoacetylamino,isopropylcarbonylamino, tert.-butyloxycarbonylamino,methylsulphonylamino, benzoylamino, phenylamino, 1-naphthylamino,4-nitro-2-pyridyl-amino, cyano, ethoxycarbonyl, aminocarbonyl,methylaminocarbonyl, dimethylaminocarbonyl, 2-hydroxy-1-ethoxy,2-(2-amino-1-ethoxy)-1-ethoxy, 2-(2-hydroxy-1-ethoxy)-1-ethoxy,2-amino-1-ethylthio, 1-methyl-2-pyrrolidinyl, 1-pyrrolidinyl,2-oxo-pyrrolidin-1-yl, 1-piperidinyl, 2-oxo-piperidin-1-yl, morpholino,4-(2-hydroxyethyl)-1-piperazinyl,2-(2-dimethylaminoethyl)-1-piperidinyl, 4-methyl-1-piperazinocarbonyl,3-carboxy-2-methoxy-phenyl, 2-hydroxyphenyl, 3-hydroxyphenyl,4-hydroxyphenyl, 4-(aminosulphonyl)phenyl, 4-nitrophenyl-,3-methoxycarbonylphenyl, 2-(2-amino-1-ethyl)phenyl, 4-pyridyl,1H-imidazol-1-yl-, 1H-imidazol-4-yl, 1H-pyrazol-4-yl,1-methyl-1H-pyrrol-2-yl, 1H-indol-3-yl, 6-methoxy-1H-benzimidazol-2-yl,4-(2H-pyridazin-3-on-6-yl)-phenyl or imidazolidin-2-on-1-yl group,

[0408] an ethyl group substituted in the 1-position by a carboxy groupand additionally substituted in the 2 position by a hydroxy,aminocarbonyl, 2-chlorophenyl, 4-chlorophenyl, 1H-imidazol-4-yl or4-hydroxyphenyl group,

[0409] an ethyl group substituted in the 1-position by an aminocarbonylgroup and additionally substituted in the 2 position by a4-methoxyphenyl group,

[0410] an ethyl group substituted in the 1-position by a4-phenyl-1-butylaminocarbonyl group and additionally substituted in the2 position by a phenyl group,

[0411] an ethyl group substituted in the 2 position by a hydroxy groupand additionally substituted in the 2 position by a phenyl,3-hydroxyphenyl, 4-hydroxyphenyl or 4-hydroxy-3-methoxyphenyl group,

[0412] an ethyl group substituted in the 1-position by a phenyl groupand additionally substituted in the 2 position by a hydroxy or carboxygroup,

[0413] an ethyl group substituted in the 1-position by a 3-pyridyl groupand additionally substituted in the 2 position by an ethoxycarbonylgroup,

[0414] an ethyl group substituted in the 1-position by a carboxy groupand additionally substituted in the 2 position by two phenyl groups,

[0415] an n-propyl group substituted in the 2 position by a hydroxygroup and additionally substituted in the 3 position by an amino,hydroxy or morpholino group,

[0416] an n-propyl group substituted in the 3 position by a methoxy,isopropylamino, methylamino, diethylamino, dibenzylamino,1-pyrrolidinyl, 1-piperidinyl, morpholino, 4-methyl-1-piperazinyl,-tert.-butyloxycarbonylamino, 2-oxo-1-pyrrolidinyl,2-oxo-piperidin-1-yl, ethoxycarbonyl, 4-pyridyl,4-amino-3,5-dichlorophenyl, 3-amino-1-propoxy,2-(3-amino-1-propoxy)-1-ethoxy, 1H-imidazol-1-yl,2-aza-bicyclo[2.2.1]hept-5-en-2-yl, 4-(3-amino-1-propyl)-1-piperazinylor 2-diethylaminomethyl-1-piperidinyl group,

[0417] an n-butyl group substituted in the 4-position by a4-hydroxyphenyl group,

[0418] an n-butyl group substituted in the 4-position by a dimethylaminogroup and additionally substituted in the 2 position by a phenyl group,

[0419] a 2-methyl-2-butyl group substituted in the 3 position by aphenylaminocarbonylamino or a 1-(4-pyridyl)-3-imidazolin-2-on-3-yl,

[0420] an n-pentyl group substituted in the 1-position by a carboxygroup and additionally substituted in the 5 position by abenzyloxycarbonylamino group,

[0421] a 1-pentyl group substituted in the 5 position by amethoxycarbonyl group and additionally substituted in the 5 position byan acetylamino group,

[0422] an n-hexyl group substituted in the 6 position by a hydroxy,amino, tert.-butyloxycarbonylamino or N-methyl-N-phenethylamino group,

[0423] a cyclohexyl group substituted in the 2 position by a hydroxy,amino, dimethylamino or hydroxymethyl group,

[0424] a cyclohexyl group substituted in the 3 position by an amino orcarboxy group,

[0425] a cyclohexyl group substituted in the 4-position by a hydroxy,amino, carboxy, 2-carboxyethyl, 3-carboxypropyl, methoxycarbonyl ordimethylamino group,

[0426] a cyclohexylmethyl group substituted in the 3 position of thecyclohexyl moiety by an aminomethyl or atert.-butyloxycarbonylaminomethyl group,

[0427] a cyclohexylmethyl group substituted in the 4-position of thecyclohexyl moiety by an aminomethyl, dimethylaminomethyl or2-carboxyethyl group,

[0428] a 4-piperidinyl group substituted in the 1-position by a methyl,benzyl or phenylsulphonyl group,

[0429] a 1-methyl-4-carboxy-4-piperidinyl group,

[0430] a 1-ethyl-3-piperidinyl, 1-benzyl-3-pyrrolidinyl or5-(3-carboxy-1-propyl)-indan-2-yl) group, and

[0431] R_(e) denotes a bromine atom or a methyl, ethyl, ethynyl,trifluoromethyl, methylsulphenyl, trifluoromethylsulphenyl, cyano ornitro group,

[0432] optionally in the form of the tautomers, racemates, enantiomers,diastereomers and mixtures thereof, and optionally also thepharmacologically acceptable acid addition salts thereof.

[0433] Most preferred are the compounds of formula I wherein R_(a)denotes hydrogen.

[0434] Particularly preferred are those compounds of formulae 1 to 5,wherein:

[0435] R_(b) denotes a phenyl group optionally substituted in the 4position of the phenyl moiety by a fluorine, chlorine or bromine atom,by a cyano, aminosulphonyl, dimethylaminosulphonyl, carboxy,piperidinomethyl, 1,2,4,5-tetrahydro-benzo[d]azepin-3-yl-methyl,2-carboxy-1-ethyl, phenylaminocarbonyl, benzylaminocarbonyl,aminocarbonyl, methoxycarbonyl, (N-methyl-N-methylsulphonyl)amino,diethylaminomethyl, 3-diethylamino-1-propyloxy, morpholino,4-methyl-1-piperazinyl, 2-H-tetrazol-5-yl, 1-H-imidazol-4-yl, or nitrogroup, or a phenyl group substituted in the 3 position of the phenylmoiety by a chlorine or bromine atom, a cyano, aminocarbonyl, carboxy,ethoxycarbonyl or nitro group or a group of the formula

—CH₂—NH—CH₂—C_(2s)F_(2s+1)

[0436] wherein s denotes 1 or 2,

[0437] or a 3,4-dichlorophenyl, 3,5-dichlorophenyl,4-amino-3,5-dichlorophenyl, 3-chloro-4-fluorophenyl,4-chloro-3-methylphenyl, 4-chloro-3-trifluoromethylphenyl,4-bromo-3-chlorophenyl, 3-hydroxy-4-methylphenyl group,benzotriazol-5-yl, benzimidazol-5-yl, indazol-5-yl or indazol-6-yl or agroup of the formula

[0438] wherein s denotes 1 or 2.

[0439] Most preferred of all are compounds of formula I wherein Redenotes a trifluoromethyl, ethyl, ethynyl or nitro group, particularly atrifluoromethyl or nitro group.

[0440] The best results are achieved with compounds of formula Iwherein:

[0441] the group R_(c)NR_(d)

[0442] is selected from the following groups:

[0443] 2-amino-1-ethylamino, 2-acetylamino-ethylamino,2-aminocarbonyl-1-ethylamino, 2-methoxy-1-ethylamino,2-morpholino-1-ethylamino, 3-aminopropyl-amino, 1-carboxy-2-propylamino,4-aminobutylamino, 5-hydroxy-1-pentylamino,3-(3-aminopropoxy-1-propylamino, 2-(3-hydroxyphenyl)-1-ethyl-amino,2-(4-hydroxy-3-methoxy-phenyl)-2-hydroxy-1-ethylamino,2-(2-(2-amino-1-ethyl)-phenyl)-1-ethyl-amino, 4-hydroxy-cyclohexylamino,3-amino-cyclohexylamino, 4-aminomethyl-cyclohexylmethylamino,4-dimethylamino-cyclohexylamino, 1-methyl-piperidin-4-yl-methylamino,N-(4-methyl-piperidin-4-yl)-N-methyl-amino,3-(2-oxo-pyrrolidin-1-yl)-propyl-1-amino,1,4,6,7-tetrahydro-imidazo[4,5-c]pyridin-5-yl,2-hydroxymethyl-pyrrolidin-1-yl, 4-aminomethyl-piperidin-1-yl,3-hydroxymethyl-piperidin-1-yl, 3-acetylaminomethyl-piperidin-1-yl,4-(N-acetyl-N-methyl-aminomethyl)-piperidin-1-yl,3-(4-(pyrrolidin-1-yl)butyl)-piperidin-1-yl,3-(2-aza-bicyclo[2.2.1]hept-5-en-2-yl)-propylamino and7-methyl-2,7-diaza-spiro[4.4]non-2-yl.

[0444] The invention further relates to the physiologically acceptablesalts of the compounds of the formula.

[0445] The invention also relates to the compounds of formula I for useas pharmaceutical compositions.

[0446] In another aspect the invention relates to a process forpreparing the compounds of formula I, wherein

[0447] a. a compound of general formula

[0448]  wherein

[0449] R_(c) to R_(e) are as hereinbefore defined and

[0450] Z₁ denotes a leaving group,

[0451] is reacted with an amine of general formula

H—(R_(a)NR_(b))  (III)

[0452]  wherein

[0453] R_(a) and R_(b) are as hereinbefore defined; or

[0454] b. a compound of general formula IV

[0455]  wherein

[0456] R_(a), R_(b) and R_(e) are as hereinbefore defined, and

[0457] Z₂ denotes a leaving group, is reacted with an amine of generalformula

H—(R_(c)NR_(d))  (V)

[0458]  wherein

[0459] R_(c) and R_(d) are as hereinbefore defined.

[0460] The reaction is expediently carried out in a solvent such asethanol, isopropanol, butanol, tetrahydrofuran, dioxan, toluene,chlorobenzene, dimethylformamide, dimethylsulphoxide,ethylenglycolmonomethylether, ethylenglycoldiethylether or sulpholaneoptionally in the presence of an inorganic base, e.g. sodium carbonateor potassium hydroxide, or a tertiary organic base, e.g. triethylamine,N-ethyl-diisopropylamine or pyridine, while the latter maysimultaneously also act as solvent, and optionally in the presence of areaction accelerator such as a copper salt, a correspondingamine-hydrohalide or alkali metal halide at temperatures between 0 and250° C., preferably however at temperatures between 20 and 200° C. Thereaction may however also be carried out without a solvent or in anexcess of the compound of formula III or V used.

[0461] Moreover the compounds of general formula I obtained as mentionedhereinbefore may be resolved into their enantiomers and/ordiastereomers. Thus, for example, cis-/trans mixtures may be resolvedinto their cis- and trans-isomers, and compounds with at least oneoptically active carbon atom are resolved into their enantiomers.

[0462] Thus, for example, the cis/trans mixtures obtained may beresolved by chromatography into the cis and trans isomers thereof, thecompounds of general formula I obtained which occur as racemates may beseparated by methods known per se (cf. Allinger N. L. and Eliel E. L. in“Topics in Stereochemistry”, Vol. 6, Wiley Interscience, 1971) intotheir optical antipodes and compounds of general formula I with at least2 asymmetric carbon atoms may be resolved into their diastereomers onthe basis of their physical-chemical differences using methods known perse, e.g. by chromatography and/or fractional crystallisation, and, ifthese compounds are obtained in racemic form, they may subsequently beresolved into the enantiomers as mentioned above.

[0463] The enantiomers are preferably separated by column separation onchiral phases or by recrystallisation from an optically active solventor by reacting with an optically active substance which forms salts orderivatives such as e.g. esters or amides with the racemic compound,particularly acids and the activated derivatives or alcohols thereof,and separating the diastereomeric mixture of salts or derivatives thusobtained, e.g. on the basis of their differences in solubility, whilstthe free antipodes may be released from the pure diastereomeric salts orderivatives by the action of suitable agents. Optically active acids incommon use are e.g. the D- and L-forms of tartaric acid ordibenzoyltartaric acid, di-o-tolyltartaric acid, malic acid, mandelicacid, camphorsulphonic acid, glutamic acid, N-acetylglutamic acid,aspartic acid, N-acetylaspartic acid or quinic acid. An optically activealcohol may be for example (+)- or (−)-menthol and an optically activeacyl group in amides, for example, may be a (+)- or(−)-menthyloxycarbonyl group.

[0464] Furthermore, the compounds of formula I obtained may be convertedinto the salts thereof, particularly for pharmaceutical use into thephysiologically acceptable salts with inorganic or organic acids. Acidswhich may be used for this purpose include for example hydrochloricacid, hydrobromic acid, sulphuric acid, phosphoric acid, fumaric acid,succinic acid, lactic acid, citric acid, tartaric acid or maleic acid.

[0465] Moreover, if the new compounds of formula I thus obtained containan acid group such as a carboxy group, they may subsequently, ifdesired, be converted into the salts thereof with inorganic or organicbases, particularly for pharmaceutical use into the physiologicallyacceptable salts thereof. Suitable bases for this purpose include forexample sodium hydroxide, potassium hydroxide, arginine,cyclohexylamine, ethanolamine, diethanolamine and triethanolamine.

[0466] The compounds of general formulae II to V used as startingmaterials are known from the literature in some cases or may be obtainedby methods known from the literature.

[0467] As already mentioned, the compounds of formula I according to theinvention and the physiologically acceptable salts thereof have valuablepharmacological properties, particularly an inhibitory effect on theproliferation of cells, particularly endothelial cells. This effect ofthe new compounds was tested by the following standard procedure, asfollows:

[0468] The invention also relates to the use of compounds of formula (I)for preparing a medicament for the treatment and prevention of diseasescharacterised by excessive or anomalous cell proliferation, as well aspharmaceutical compositions which are characterised by a content of oneor more compounds of formula I.

[0469] Some procedures for preparing the compounds according to theinvention will be described in detail hereinafter by way of example. Thefollowing Examples of synthesis are intended solely as a detailedillustration without restricting the object of the invention thereto.

[0470] Preparation of the Starting Compounds:

[0471] The following starting compounds may be prepared according to thereference cited in each case:

[0472] Synthesis of 2-chloro-4-thiocyanato-5-nitro-pyrimidine: Takahashiet al., Chem. Pharm. Bull. (1958) 334

[0473] Synthesis of 2,4-dichloro-5-trifluoromethylsulphanyl-pyrimidine:Haas, A.; Lieb, M.; J. Heterocycl. Chem. (1986) 1079-1084;

[0474] 2,4-dichloro-5-methylsulphanyl-pyrimidine:

[0475] a) Ishikawa, Katsutoshi et al.; Preparation and fungicidalactivity of halothiocyanopyrimidines. JP 62 053973

[0476] b) Maggiali, C. et al., Farmaco, Ed. Sci. (1988), 43(3), 277-91.

[0477] Synthesis of 2,4-dichloro-5-trifluoromethyl-pyrimidine: Shen;Lewis; Ruyle; J. Org. Chem. 30 (1965) 835

[0478] Synthesis of 2,4-dichloro-5-nitro-pyrimidine: Albert et al.; J.Chem. Soc. (1951) 474

[0479] Synthesis of 4,5,6,7-tetrahydro-1(3)H-imidazo[4,5-c]pyridine:Dale; Dudley; J. Pharmacol. exper. Therap.; 18; 106; Chem. Zentralbl.;GE; 93; I; 1922; 770. Lit 2: Fraenkel; Zeimer; Biochem. Z.; 110; 1920;238.

[0480] Synthesis of (N-(trans-4-hydroxy-cyclohexyl)-N-methyl-amine: U.S.Pat. No. 2,152,960.

[0481] HPLC Methods

[0482] Method A: The HPLC/MS data were obtained using an HP-1100-MSDapparatus.

[0483] The following was used as the mobile phase:

[0484] A: water with 0.1% formic acid

[0485] B: acetonitrile with 0.1% formic acid time in min % A % B flowrate in ml/min 0.0 95 5 0.400 0.5 95 5 0.400 5.5 5 95 0.400 8.5 5 950.400 9.5 95 5 0.400

[0486] The stationary phase used was a Waters X-Terra™ MS C₁₈ column,2.5 μm, 2.1 mm×50 mm (column temperature: constant at 30° C. (±0.5° C.))

[0487] The UV detection was carried out at two wavelengths: signal A at230 nm (+2 nm), signal B at 254 nm (±2 nm).

[0488] Range of mass-spectrometric detection: m/z 100 to m/z 1000

[0489] Method B:

[0490] ThermoFinnigan LCQ Deca, Surveyor-HPLC

[0491] The following was used as the mobile phase:

[0492] A: water with 0.1% trifluoroacetic acid

[0493] B: acetonitrile with 0.1% trifluoroacetic acid time in min % A %B flow rate in ml/min 0.0 95 5 0.500 4.5 2 98 0.500 5.5 2 98 0.500 5.695 5 0.500 7.0 95 5 0.500

[0494] The stationary phase used was a Waters X-Terra™ MS C₁₈ column,2.5 μm, 2.1 mm×50 mm (column temperature: constant at 40° C.)

[0495] The diode array detection was carried out in a wavelength rangefrom 210-500 nm Range of mass-spectrometric detection: m/z 150 to m/z1500

[0496] Method C:

[0497] Analogous to method B with the gradient: time in min % A % B flowrate in ml/min 0.0 95 5 0.6 4.0 5 95 0.6 6.0 5 95 0.6 8.0 95 5 0.6 1 minpost run 95 5 0.6

[0498] Method D:

[0499] Analogous to Method B with the gradient: time in min % A % B flowrate in ml/min 0.0 95 5 0.4 5.5 5 95 0.4 9.5 5 95 0.4 3 min post run 955 0.4

[0500] Method E:

[0501] Analogous to Method B with the gradient: time in min % A % B flowrate in ml/min 0.0 90 10 0.7 4.0 5 95 0.7 4.5 5 95 0.7 6.0 90 10 0.7

[0502] Method F:

[0503] The mobile phase used was:

[0504] A: water containing 0.1% formic acid

[0505] B: Acetonitrile containing 0.1% formic acid time in min % A % Bflow rate in ml/min 0.5 95 5 1.5 5.0 0 100 1.5

[0506] The stationary phase used was a Develosil RPAqueous 4.6×50 mmcolumn. UV detection was carried out at 254 nm

[0507] Method G:

[0508] Analogous to Method F with the gradient: time in min % A % B flowrate in ml/min 0.5 90 10 1.5 5.0 0 100 1.5

[0509] Method H:

[0510] Analogous to Method F with the gradient: time in min % A % B flowrate in ml/min 0.5 80 20 1.5 5.0 0 100 1.5

[0511] Method I:

[0512] Analogous to Method F with the gradient: time in min % A % B flowrate in ml/min 0.5 70 30 1.5 5.0 0 100 1.5

[0513] Method J:

[0514] Analogous to Method F with the gradient: time in min % A % B flowrate in ml/min 0.5 95 5 1.5 4.5 70 30 1.5 5.0 0 100 1.5

[0515] Method K:

[0516] Analogous to Method F with the gradient: time in min % A % B flowrate in ml/min 0.5 60 40 1.5 5.0 0 100 1.5

[0517] Method L:

[0518] Analogous to Method F with the gradient: time in min % A % B flowrate in ml/min 0.5 40 60 1.5 5.0 0 100 1.5

[0519] Method M:

[0520] Analogous to Method F with the gradient: time in min % A % B flowrate in ml/min 0.5 30 70 1.5 5.0 0 100 1.5

EXAMPLE I

[0521] 2-(3,4-dichlorophenylamino)-4-thiocyanato-5-nitro-pyrimidine

[0522] 2.47 g of 3,4-dichloroaniline in 12 ml ethanol are added to 3.00g of 2-chloro-4-thiocyanato-5-nitro-pyrimidine in 40 ml toluene atambient temperature. The mixture is stirred for another 16 hours, thesolid is suction filtered, washed twice with 30 ml toluene and then oncewith 30 ml of ethanol and dried.

[0523] Yield: 2.86 g (60% of theory), Melting point: 240-242° C.

[0524] The following compounds are obtained analogously to Example I:

[0525] (1)2-(4-amino-3,5-dichlorophenylamino)-4-thiocyanato-5-nitro-pyrimidine

[0526] (2)2-(4-aminosulphonyl-phenylamino)-4-thiocyanato-5-nitro-pyrimidine

[0527] (3) 2-(4-chlorophenylamino)-4-thiocyanato-5-nitro-pyrimidine

[0528] Melting point: 224-226° C.

[0529] (4) 2-(4-carboxyphenylamino)-4-thiocyanato-5-nitro-pyrimidine

[0530] (5)2-(3-chloro-4-fluoro-phenylamino)-4-thiocyanato-5-nitro-pyrimidine

[0531] (6)2-(3-aminocarbonyl-phenylamino)-4-thiocyanato-5-nitro-pyrimidine

[0532] (7)2-(4-phenylaminocarbonyl-phenylamino)-4-thiocyanato-5-nitro-pyrimidine

[0533] (8) 2-(4-nitro-phenylamino)-4-thiocyanato-5-nitro-pyrimidine

[0534] (9) 2-(4-cyano-phenylamino)-4-thiocyanato-5-nitro-pyrimidine

[0535] (10) 2-(3-bromo-phenylamino)-4-thiocyanato-5-nitro-pyrimidine

[0536] (11) 2-(4-bromo-phenylamino)-4-thiocyanato-5-nitro-pyrimidine

[0537] (12) 2-(3-nitro-phenylamino)-4-thiocyanato-5-nitro-pyrimidine

[0538] (13)2-(4-(2-carboxy-1-ethyl)phenylamino)-4-thiocyanato-5-nitro-pyrimidine

[0539] (14)2-(4-aminocarbonyl-phenylamino)-4-thiocyanato-5-nitro-pyrimidine

[0540] (15)2-(4-chloro-3-methyl-phenylamino)-4-thiocyanato-5-nitro-pyrimidine

[0541] (16)2-(4-methoxycarbonyl-phenylamino)-4-thiocyanato-5-nitro-pyrimidine

[0542] (17) 2-(3-cyano-phenylamino)-4-thiocyanato-5-nitro-pyrimidine

[0543] (18)2-(4-benzylaminocarbonyl-phenylamino)-4-thiocyanato-5-nitro-pyrimidine

[0544] (19) 2-(4-fluoro-phenylamino)-4-thiocyanato-5-nitro-pyrimidine

[0545] (20) 2-(benzylamino)-4-thiocyanato-5-nitro-pyrimidine

[0546] (21) 2-(2-chlorobenzylamino)-4-thiocyanato-5-nitro-pyrimidine

[0547] (22) 2-(3-carboxyphenylamino)-4-thiocyanato-5-nitro-pyrimidine

[0548] (23)2-(3-ethoxycarbonyl-phenylamino)-4-thiocyanato-5-nitro-pyrimidine

EXAMPLE II

[0549]2-chloro-4-(2-acetylamino-ethylamino)-5-trifluoromethyl-pyrimidine

[0550] 1.84 g of 2-acetylamino-ethylamine dissolved in 10 ml of dioxaneare added to 3.91 g of 2,4-dichloro-5-trifluoromethyl-pyrimidine in 20ml dioxane at ambient temperature. Then 3.7 ml of 5 M potassiumcarbonate solution are added and the mixture is stirred for three daysat ambient temperature. It is then filtered through Alox B and washedwith dioxane. The filtrate is concentrated by evaporation and theresidue separated by chromatography through a silica gel column withcyclohexane:ethyl acetate: methanol (5:4:1).

[0551] Yield: 2.30 g (45% of theory); Melting point: 185° C.

[0552] The following compounds are obtained analogously to Example II:

[0553] (1) 2-chloro-4-(2-acetylamino-ethylamino)-5-nitro-pyrimidine

[0554] Prepared from 2,4-dichloro-5-nitro-pyrimidine in the presence of2N sodium hydroxide solution.

[0555] (2)2-chloro-4-(2-acetylamino-ethylamino)-5-methylsulphanyl-pyrimidine

[0556] Prepared from 2,4-dichloro-5-methylsulphanyl-pyrimidine.

[0557] (3)2-chloro-4-(2-acetylamino-ethylamino)-5-trifluoromethylsulphanyl-pyrimidine

[0558] R_(f)=0.15 (silica gel; methylene chloride:methanol=20:1)

[0559] Prepared from 2,4-dichloro-5-trifluoromethylsulphanyl-pyrimidine.

[0560] (4) 2-chloro-4-(2-acetylamino-ethylamino)-5-bromo-pyrimidine

[0561] Prepared from 2,4-dichloro-5-bromo-pyrimidine.

[0562] R_(f)=0.16 (silica gel; ethyl acetate:cyclohexane=1:1)

[0563] (5)2-chloro-4-(N-(trans-4-hydroxy-cyclohexyl)-N-methyl-amino)-5-nitro-pyrimidine

[0564] (6)2-chloro-4-(trans-4-hydroxy-cyclohexylamino)-5-nitro-pyrimidine

[0565] (7) 2-chloro-4-(2-pyridyl-methylamino)-5-nitro-pyrimidine

[0566] (8) 2-chloro-4-(ethoxycarbonyl-methylamino)-5-nitro-pyrimidine

[0567] (9)2-chloro-4-[N-(2-hydroxyethyl)-N-methyl-amino]-5-nitro-pyrimidine

[0568] (10)N-[2-(2-Chloro-5-trimethylsilanylethynyl-pyrimidin-4-ylamino)-ethyl]acetamide

[0569] UVmax (ethanol)=215, 265, 314 nm

[0570]¹H-NMR(D₆-DMSO, 400 MHz) δ: 0.27 (s, 9H), 1.82 (s, 3H), 3.26 (m,2H), 3.43 (m, 2H), 7.50 (t, 1H), 8.08 (t, 1H), 8.14 (s, 1H).

[0571] (11)2-chloro-4-[3-(2-oxo-pyrrolidin-1-yl)-propylamino]-5-bromo-pyrimidine

[0572] 5.0 g 5-bromo-2,4-dichloro-pyrimidine are placed in 50 ml of1,4-dioxane together with 3.1 g of 1-(3-aminopropyl)-pyrrolidin-2-one.At ambient temperature 4.39 ml of 5 M potassium carbonate solution areadded and the mixture is stirred for 1 hour. Then the reaction mixtureis evaporated down completely, taken up in methanol, filtered throughaluminium oxide and evaporated down again. The crystalline residue istaken up in 170 ml ethyl acetate, filtered, concentrated by evaporationand recrystallised from ethyl acetate. 5.45 g (75%) of the desiredproduct are obtained.

[0573] Rf (methylene chloride/methanol=9:1; SiO2)=0.51;(M+H)⁺=333/335/337 (Cl, Br);

[0574] 1H-NMR (D6-DMSO, 400 MHz) δ: 1.72 (quint, 2H), 1.95 (quint, 2H),2.22 (t, 2H), 3.20 (t, 2H), 3.28-3.40 (m, 4H), 7.71 (t, 1H), 8.22 (s,1H).

[0575] (12) 2-chloro-4-(2-acetylamino-ethylamino)-5-methyl-pyrimidine

[0576] 1.0 g of 2,4-dichloro-5-methyl-pyrimidine is placed in DMA (0.1M) and combined at 0° C. with a solution of 0.69 g (1.2 eq.) ofN-acetylethylenediamine and 2.0 ml (2 eq.) of ethyldiisopropylamine inDMA. The reaction mixture is stirred for 1-2 hours at ambienttemperature and then evaporated to dryness. After the addition ofsaturated sodium hydrogen carbonat solution the mixture is extractedwith ethyl acetate and the organic phase is then dried over sodiumsulphate and evaporated down. To purify it further the crude product ischromatographed on silica gel. 78% of the desired product are obtained.

[0577] 1H-NMR (D6-DMSO, 300 MHz) 6:1.80 (s, 3H), 1.94 (s, 3H), 3.23 (m,2H), 3.36 (m, 2H), 7.31 (s, 1H), 7.77 (s, 1H), 7.97 (s, 1H).

[0578] (13)2-chloro-4-(2-acetylamino-ethylamino)-5-chloro-pyrimidine2-chloro-4-(2-acetylamino-ethylamino)-5-chloro-pyrimidineis obtained analogously to II (12) from 2,4,5-trichloro-pyrimidine in ayield of 58%.

[0579] HPLC/MS (method F): RT=3.40 min.; [M+H]+=249/251; Abs. λmax=247,5 nm

[0580] 1H-NMR (D6-DMSO, 300 MHz) δ: 8.15 (s, 1H); 8.00-7.92 (m, 2H,N—H); 3.40 (q, J=5.8 Hz, 2H); 3.24 (q, J=5.8 Hz, 2H); 1.79 (s, 3H).

[0581] (14) 2-chloro-4-(2-acetylamino-ethylamino)-5-methoxy-pyrimidine

[0582] 1.0 g of 2,4-dichloro-5-methoxy-pyrimidine is quickly added to asolution of 0.69 g (1.2 eq.) of N-acetylethylenediamine and 1.2 ml (1.25eq.) of ethyldiisopropylamine in 20 ml of ethanol. The reaction mixtureis stirred for 2-15 hours at ambient temperature and then evaporated todryness. After the addition of ethyl acetate the mixture is extractedwith saturated sodium hydrogen carbonate solution and saturated sodiumchloride solution and the organic phase is then dried over sodiumsulphate. For further purification the crude product is chromatographedon silica gel. 793 mg (58%) of the desired product are obtained.

[0583] 1H-NMR (D6-DMSO, 300 MHz) δ: 1.79 (s, 3H), 3.21 (q, 2H), 3.34 (q,2H), 3.83 (s, 3H), 7.53 (t, 1H), 7.67 (s, 1H), 7.96 (t, 1H).

[0584] (15)2-chloro-4-(1,4,6,7-tetrahydro-imidazo[4,5-c]pyridin-5-yl)-5-chloro-pyrimidine2-chloro-4-(1,4,6,7-tetrahydro-imidazo[4,5-c]pyridin-5-yl)-5-chloro-pyrimidineis obtained analogously to II (12) from 2,4,5-trichloro-pyrimidine in ayield of 20%.

[0585] HPLC/MS (Method F): RT=3.35 min.; [M+H]+=270/272; Abs. λmax=211,4 nm

[0586] 1H-NMR (D6-DMSO, 300 MHz) δ: 12.0 (bs, 1H); 8.30 (s, 1H); 7.49(s, 1H); 4.59 (m, 2H); 3.94 (m, 2H); 2.79 (m, 2H).

[0587] (16)2-chloro-4-(2-acetylamino-ethylamino)-5-methylsulphonyl-pyrimidine2-chloro-4-(2-acetylamino-ethylamino)-5-methylsulphonyl-pyrimidine isobtained analogously to II (14) from2,4-dichloro-5-methylsulphonyl-pyrimidine in a yield of 50%.

[0588] 1H-NMR (D6-DMSO, 300 MHz) δ: 1.79 (s, 3H), 3.16-3.29 (m, 5H),3.53 (q, 2H), 7.84 (t, 1H), 7.99 (t, 1H), 8.41 (s, 1H).

[0589] (17)2-chloro-4-(2-acetylamino-ethylamino)-5-dimethylamino-pyrimidine2-chloro-4-(2-acetylamino-ethylamino)-5-dimethylamino-pyrimidine isobtained analogously to II (14) from2,4-dichloro-5-dimethylamino-pyrimidine in a yield of 49%.

[0590] 1H-NMR (D6-DMSO, 300 MHz) 6:1.80 (s, 3H), 2.57 (s, 6H), 3.24 (q,2H), 3.38 (q, 2H), 7.30 (t, 1H), 7.71 (s, 1H), 7.97 (t, 1H).

[0591] (18)2-chloro-4-(2-acetylamino-ethylamino)-5-isopropoxy-pyrimidine2-chloro-4-(2-acetylamino-ethylamino)-5-isopropoxy-pyrimidine isobtained analogously to II (14) from2,4-dichloro-5-isopropoxy-pyrimidine in a yield of 66%.

[0592] 1H-NMR (D6-DMSO, 300 MHz) δ: 1.28 (d, 6H), 1.80 (s, 3H), 3.22 (q,2H), 3.35 (q, 2H), 4.58 (sept, 1H), 7.35 (t, 1H), 7.69 (s, 1H), 7.98 (t,1H).

[0593] (19) 2-chloro-4-(2-acetylamino-ethylamino)-5-isopropyl-pyrimidine2-chloro-4-(2-acetylamino-ethylamino)-5-isopropyl-pyrimidine is obtainedanalogously to II (14) from 2,4-dichloro-5-isopropyl-pyrimidine in ayield of 70%.

[0594] 1H-NMR (D6-DMSO, 300 MHz) δ: 1.15 (d, 6H), 1.81 (s, 3H), 2.82(sept, 1H), 3.23 (q, 2H), 3.39 (q, 3H), 7.41 (t, 1H), 7.84 (s, 1H), 7.99(t, 1H).

[0595] (20)2-chloro-4-[3-(2-oxo-pyrrolidin-1-yl)-propylamino]-5-chloro-pyrimidine2-chloro-4-[3-(2-oxo-pyrrolidin-1-yl)-propylamino]-5-chloro-pyrimidineis obtained analogously to II (12) from 2,4,5-trichloro-pyrimidine in ayield of 68%.

[0596] HPLC/MS (Method F): RT=3.96 min.; [M+H]+=289/291; Abs. λmax=249,4 nm

[0597] 1H-NMR (D6-DMSO, 300 MHz) δ: 8.13 (s, 1H); 7.88 (bs, 1H, N—H),3.31 (m, 4H); 3.16 (m, 2H); 2.22 (t, J=7.9 Hz, 2H); 1.93 (m, 2H); 1.72(m, 2H).

[0598] (21)2-chloro-4-[3-(2-oxo-pyrrolidin-1-yl)-propylamino]-5-methoxy-pyrimidine

[0599] 1.0 g of 2,4-dichloro-5-methoxy-pyrimidine is added quickly to asolution of 0.95 g (1.2 eq.) of 1-(3-aminopropyl)-pyrolidin-2-one and1.2 ml (1.25 eq.) of ethyldiisopropylamine in 20 ml of ethanol. Thereaction mixture is stirred for 15 hours at ambient temperature and thenevaporated to dryness. After the addition of ethyl acetate it isextracted with saturated sodium hydrogen carbonate solution andsaturated sodium chloride solution and the organic phase is then driedover sodium sulphate. For further purification the crude product ischromatographed on silica gel. 1.15 g (72%) of the desired product isobtained.

[0600] 1H-NMR (D6-DMSO, 300 MHz) δ: 1.70 (m, 2H), 1,93 (m, 2H), 2.22 (t,2H), 3.38-3.17 (m, 6H), 3.84 (s, 3H), 7.50 (m, 1H), 7.65 (s, 1H).

[0601] (22)2-chloro-4-[3-(2-oxo-pyrrolidin-1-yl)-propylamino]-5-methyl-pyrimidine2-chloro-4-[3-(2-oxo-pyrrolidin-1-yl)-propylamino]-5-methyl-pyrimidineis obtained analogously to II (12) from 2,4-dichloro-5-methyl-pyrimidinein a yield of 46%.

[0602] HPLC/MS (Method F): RT=3.15 min.; [M+H]+=269/271

[0603] 1H-NMR (D6-DMSO, 300 MHz) 6:1.72 (m, 2H), 1,93 (m, 2H), 1.96 (s,3H), 2.22 (t, 2H), 3.22 (t, 2H), 3.26-3.38 (m, 4H), 7.23 (s, 1H), 7.77(s, 1H).

[0604] (23)2-chloro-4-[3-(2-oxo-pyrrolidin-1-yl)-propylamino]-5-methylsulphonyl-pyrimidine2-chloro-4-[3-(2-oxo-pyrrolidin-1-yl)-propylamino]-5-methylsulphonyl-pyrimidineis obtained analogously to II (21) from2,4-dichloro-5-methylsulphonyl-pyrimidine in a yield of 34%.

[0605] 1H-NMR (D6-DMSO, 300 MHz) δ: 1.76 (quint, 2H), 1,94 (quint, 2H),2.32 (t, 2H), 3.23 (t, 2H), 3.26-3.49 (m, 7H), 7.84 (t, 1H), 8.39 (s,1H).

[0606] (24)2-chloro-4-[3-(2-oxo-pyrrolidin-1-yl)-propylamino]-5-dimethylamino-pyrimidine2-chloro-4-[3-(2-oxo-pyrrolidin-1-yl)-propylamino]-5-dimethylamino-pyrimidineis obtained analogously to II (21) from2,4-dichloro-5-dimethylamino-pyrimidine in a yield of 59%.

[0607] 1H-NMR (D6-DMSO, 300 MHz) δ: 1.71 (quint, 2H), 1.93 (quint, 2H),2.22 (t, 2H), 2.58 (s, 6H), 3.19-3.38 (m, 6H), 7.30 (t, 1H), 7.70 (s,1H).

[0608] (25)2-chloro-4-[3-(2-oxo-pyrrolidin-1-yl)-propylamino]-5-isopropoxy-pyrimidine2-chloro-4-[3-(2-oxo-pyrrolidin-1-yl)-propylamino]-5-isopropoxy-pyrimidineis obtained analogously to II (21) from2,4-dichloro-5-isopropoxy-pyrimidine in a yield of 83%.

[0609] 1H-NMR (D6-DMSO, 300 MHz) δ: 1.28 (d, 6H), 1.69 (quint, 2H), 1.93(quint, 2H), 2.23 (t, 2H), 3.18-3.38 (m, 6H), 4.86 (sept, 1H), 7.29 (t,1H), 7.68 (s, 1H).

[0610] (26)2-chloro-4-[3-(2-oxo-pyrrolidin-1-yl)-propylamino]-5-isopropyl-pyrimidine2-chloro-4-[3-(2-oxo-pyrrolidin-1-yl)-propylamino]-5-isopropyl-pyrimidineis obtained analogously to II (21) from2,4-dichloro-5-isopropyl-pyrimidine in a yield of 54%.

[0611] 1H-NMR (D6-DMSO, 300 MHz) 6:1.16 (d, 6H), 1.71 (quint, 2H), 1.94(quint, 2H), 2.24 (t, 2H), 2.84 (sept, 1H), 3.22 (t, 2H), 3.26-3.34 (m,4H), 7.34 (t, 1H), 7.83 (s, 1H).

[0612] (27)2-chloro-4-(4,5,7,8-tetrahydro-1H-imidazo[4,5-d]azepin-6-yl)-5-chloro-pyrimidine

[0613] 1.0 g of 2,4,5-trichloro-pyrimidine in isopropanol (0.1 M) iscombined at 0° C. with a solution of 0.69 g (1.2 eq.) of4,5,7,8-tetrahydro-1H-imidazo[4,5-d]azepine and 2 ml (2 eq.) ofethyldiisopropylamine in isopropanol. The reaction mixture is stirredfor 1-2 hours at ambient temperature and then evaporated to dryness.After the addition of saturated sodium hydrogen carbonate solution themixture is extracted with dichloromethane and ethyl acetate and theorganic phase is then dried over sodium sulphate and evaporated down.For further purification the crude product is chromatographed on silicagel. 95% of the desired product is obtained.

[0614] HPLC/MS (Method F): RT=3.32 min.; [M+H]+=284/286; Abs. λmax=260,8 nm

[0615] 1H-NMR (D6-DMSO, 300 MHz) δ: 8.18 (s, 1H); 7.37 (s, 1H);4.11-4.08 (m, 4H); 2.89-2.86 (m, 4H).

[0616] (28)2-chloro-4-(4,5,7,8-tetrahydro-1H-imidazo[4,5-d]azepin-6-yl)-5-methyl-pyrimidine2-chloro-4-(4,5,7,8-tetrahydro-1H-imidazo[4,5-d]azepin-6-yl)-5-methyl-pyrimidineis obtained analogously to II (27) from 2,4-dichloro-5-methyl-pyrimidinein a yield of 36%.

[0617] HPLC/MS (Method F): RT=3.22 min.; [M+H]+=264/266

[0618] 1H-NMR (D6-DMSO, 300 MHz) δ: 2.30 (s, 3H), 2.83 (m, 4H), 3.93 (m,4H), 7.39 (s, 1H), 7.87 (s, 1H).

[0619] (29)2-chloro-4-(1,4,6,7-tetrahydro-imidazo[4,5-c]pyridin-5-yl)-5-methyl-pyrimidine2-chloro-4-(1,4,6,7-tetrahydro-imidazo[4,5-c]pyridin-5-yl)-5-methyl-pyrimidineis obtained analogously to II (12) from 2,4-dichloro-5-methyl-pyrimidinein a yield of 26%.

[0620] HPLC/MS (Method F): RT=3.19 min.; [M+HJ+=250/252

[0621] 1H-NMR (D6-DMSO, 300 MHz) δ: 2.24 (s, 3H), 2.74 (m, 2H), 3.74 (m,2H), 4.46 (m, 2H), 7.48 (s, 1H), 8.01 (s, 1H), 11.82 (s, 1H).

[0622] (30)2-chloro-4-(1,4,6,7-tetrahydro-imidazo[4,5-c]pyridin-5-yl)-5-methoxy-pyrimidine2-chloro-4-(1,4,6,7-tetrahydro-imidazo[4,5-c]pyridin-5-yl)-5-methoxy-pyrimidineis obtained analogously to II (21) from2,4-dichloro-5-methoxy-pyrimidine in a yield of 88%.

[0623] 1H-NMR (D6-DMSO, 300 MHz) δ: 2.71 (m, 2H), 3.87 (s, 3H), 3.97 (m,2H), 4.67 (m, 2H), 7.49 (s, 1H), 7.91 (s, 1H), 11.86 (s, 1H).

[0624] (31)2-chloro-4-(4,5,7,8-tetrahydro-1H-imidazo[4,5-d]azepin-6-yl)-5-bromo-pyrimidine2-chloro-4-(4,5,7,8-tetrahydro-1H-imidazo[4,5-d]azepin-6-yl)-5-bromo-pyrimidineis obtained analogously to II (27) from 2,4-dichloro-5-bromo-pyrimidinein a yield of 98%.

[0625] HPLC/MS (Method F): RT 3.66 min.; [M+H]+=328/330/332

[0626] 1H-NMR (D6-DMSO, 300 MHz) δ: 2.89 (m, 4H), 4.12 (m, 4H), 7.36 (d,1H), 8.30 (s, 1H), 11.61 (s, 1H).

[0627] (32)2-ehloro-4-(1,4,6,7-tetrahydro-imidazo[4,5-c]pyridin-5-yl)-5-bromo-pyrimidine2-chloro-4-(1,4,6,7-tetrahydro-imidazo[4,5-c]pyridin-5-yl)-5-bromo-pyrimidineis obtained analogously to II (12) from 2,4-dichloro-5-bromo-pyrimidinein a yield of 32%.

[0628] HPLC/MS (Method F): RT=3.47 min

[0629] 1H-NMR (D6-DMSO, 300 MHz) δ: 2.80 (m, 2H), 3.94 (m, 2H), 4.58 (m,2H), 7.51 (s, 1H), 8.42 (s, 1H), 11.89 (s, 1H).

[0630] (33)2-chloro-4-(1,4,6,7-tetrahydro-imidazo[4,5-c]pyridin-5-yl)-5-dimethylamino-pyrimidine

[0631]2-chloro-4-(1,4,6,7-tetrahydro-imidazo[4,5-c]pyridin-5-yl)-5-dimethylamino-pyrimidineis obtained from 2,4-dichloro-5-dimethylamino-pyrimidine analogously toII (21) in a yield of 43%.

[0632] 1H-NMR (D6-DMSO, 300 MHz) δ: 2.64 (s, 6H), 2.76 (m, 2H), 3,97 (t,2H), 4.69 (s, 2H), 7.48 (s, 1H), 7.86 (s, 1H), 11.85 (s, 1H).

[0633] (34)2-chloro-4-(1,4,6,7-tetrahydro-imidazo[4,5-c]pyridin-5-yl)-5-isopropyl-pyrimidine2-chloro-4-(1,4,6,7-tetrahydro-imidazo[4,5-c]pyridin-5-yl)-5-isopropyl-pyrimidineis obtained analogously to II (21) from2,4-dichloro-5-isopropyl-pyrimidine in a yield of 50%.

[0634] 1H-NMR (D6-DMSO, 300 MHz) 6:1.26 (d, 6H), 2.79 (m, 2H), 3.00(sept., 1H), 3.66 (m, 2H), 4.35 (m, 2H), 7.50 (s, 1H), 8.30 (s, 1H),11.88 (s, 1H).

EXAMPLE III

[0635] 2-(3.4-dichlorophenylamino)-4-chloro-5-trifluoromethyl-pyrimidine

[0636] 4.86 g of 3,4-dichloroaniline dissolved in 10 ml of dioxane areadded to 6.51 g of 2,4-dichloro-5-trifluoromethyl-pyrimidine in 40 ml ofdioxane at ambient temperature. Then 6 ml of 5 M potassium carbonatesolution are added and the mixture is stirred for three days at ambienttemperature. It is then filtered through Alox B (20 ml) and washed withdioxane. The filtrate is concentrated by evaporation, the residuedissolved in 50 ml methylene chloride and this solution is cooled in abath of dry ice and acetone. The precipitate is suction filtered and thefiltrate is cooled again. After suction filtering again the precipitatesare combined and the filtrate is concentrated by evaporation. Theresidue is separated by chromatography through an RP 18 column(gradient: acetonitrile: H2O=20:80 to 80:20).

[0637] The precipitates and the product obtained by chromatography ofthe filtrate are combined.

[0638] Yield: 3.90 g (38% of theory)

[0639] The following compounds are obtained analogously to Example III:

[0640] (1) 2-(3-chlorophenylamino)-4-chloro-5-trifluoromethyl-pyrimidine

[0641] (2) 2-(phenylamino)-4-chloro-5-trifluoromethyl-pyrimidine

[0642] (3) 2-(4-chlorophenylamino)-4-chloro-5-trifluoromethyl-pyrimidine

[0643] R_(f)=0.88 (silica gel; methylene chloride)

[0644] (4) 2-(4-bromophenylamino)-4-chloro-5-trifluoromethyl-pyrimidine

[0645] (5) 2-(3-bromophenylamino)-4-chloro-5-trifluoromethyl-pyrimidine

[0646] (6)2-(4-carboxyphenylamino)-4-chloro-5-trifluoromethyl-pyrimidine

[0647] (7)2-(4-(2-carboxy-1-ethyl-)phenylamino)-4-chloro-5-trifluoromethyl-pyrimidine

[0648] (8) 2-(2-naphthylamino)-4-chloro-5-trifluoromethyl-pyrimidine

[0649] (9)2-(3,5-dichlorophenylamino)-4-chloro-5-trifluoromethyl-pyrimidine

[0650] (10)2-(4-(1-piperidinyl-methyl-)phenylamino)-4-chloro-5-trifluoromethyl-pyrimidine

[0651] Prepared using 4-(piperidin-1-yl-)-methyl-aniline. Thechromatography was carried out using silica gel.

[0652] (11) 2-(3,4-dichlorophenylamino)-4-chloro-5-cyano-pyrimidine

[0653] Prepared using of 2,4-dichloro-5-cyano-pyrimidine.

[0654] (12)2-[4-(1,2,4,5-tetrahydro-benzo[d]azepin-3-yl-methyl)-phenylamino]-4-chloro-5-trifluoromethyl-pyrimidine

[0655] (13) (6)2-(4-aminocarbonylphenylamino)-4-chloro-5-trifluoromethyl-pyrimidine

EXAMPLE IV

[0656] 4-(3,5-dimethyl-piperazin-1-sulphonyl)-phenylamine

[0657] 3 g of 4-nitrobenzenesulphonylchloride are dissolved in 100 ml ofdioxane, and 1.56 g of 2,6-dimethylpiperazine and 2.8 ml of a 5 Maqueous potassium carbonate solution are pipetted in. The mixture isstirred at ambient temperature for 3 hours. The precipitate formed isfiltered off, rinsed with fresh dioxane and the combined organicsolution is evaporated down.

[0658] Yield 3.3 g

[0659] Rf value 0.26 (silica gel, dichloromethane: methanol=95:5)

[0660] The intermediate product4-(3,5-dimethyl-piperazin-1-sulphonyl)-nitrobenzene is taken up in 25 mlof ethanol and combined with 0.3 g of palladium on charcoal (10%). Atambient temperature and under 5 bars of hydrogen the mixture ishydrogenated until total conversion is achieved. After the catalyst hasbeen filtered off and the solvent eliminated, the product is obtained asa yellowish solid.

[0661] Yield: 3.0 g

[0662] Rf value 0.19 (silica gel, dichloromethane: methanol=95:5)

EXAMPLE V

[0663]4-(4-tert-butyl-oxycarbonyl-homo-piperazin-1-sulphonyl)-phenylamine

[0664] 2.8 g of 4-nitrobenzenesulphonylchloride are placed in 90 mldichloromethane and to this are added dropwise 5 g ofN-(tert.-butyl-oxycarbonyl)-homopiperazine and 5.1 ml of triethylamine.The mixture is stirred at ambient temperature for 1.5 hours. The organicsolution is washed with 1 M aqueous sodium acetate and water and thenconcentrated by evaporation.

[0665] Yield 4.8 g

[0666] Rf value 0.61 (silica gel, dichloromethane: methanol=95:5)

[0667] The intermediate product is taken up in 25 ml of methanol and 10ml of ethanol and combined with 0.5 g of palladium on charcoal (10%). Atambient temperature and under 5 bars of hydrogen the mixture ishydrogenated until fully converted. After the catalyst has been filteredoff and the solvent eliminated, the product is obtained as a yellowishsolid.

[0668] Yield: 3.9 g

[0669] Rf value 0.41 (silica gel, dichloromethane: methanol=95:5)

EXAMPLE VI

[0670] 1-[2-(methylamino)-ethyl]-pyrrolidin-2-onee

[0671] 48 ml of N-methyl-ethylenediamine and 42 ml of butyrolactone areheated together to 250° C. for 7 hours in an autoclave. The productdistils out of the resulting brown oil at 150-155° C. and at 0.01 Torr.Yield 8.8 g

[0672] Rf value 0.29 (silica gel, ethyl acetate: methanol=1:1)

EXAMPLE VII

[0673] 4-(N-methyl-N-methylsulphonyl-amino)-phenylamine

[0674] 4.3 g of 4-(N-methylsulphonylamino)-nitrobenzene are dissolved in40 ml of DMSO and stirred with 2,5 g of potassium-tert-butoxide for 1hour at RT. 4.2 g of methyl iodide in 10 ml of DMSO are added dropwiseto the solution and stirred overnight at ambient temperature. Themixture is then poured onto about 120 ml of ice water and extracted withethyl acetate. The organic phase is washed with water three times, thendried over sodium sulphate and concentrated by evaporation. The residueis triturated with diethylether, suction filtered and dried. Yield: 4.6g

[0675] Melting point 105-106° C.

[0676] Rf value 0.52 (silica gel, toluene: ethyl acetate=7:3)

[0677] 4.1 g of 4-(N-methyl-N-methylsulphonyl-amino)-nitrobenzene aretaken up in 80 ml of methanol, combined with 1 g of palladium charcoaland hydrogenated at ambient temperature under 5 bar. After 30 minutesthe catalyst is filtered off, the mixture is evaporated down and theremaining product is triturated with diethylether. Yield: 3.6 g

[0678] Melting point 116° C.

[0679] Rf value 0.14 (silica gel, toluene: ethyl acetate=7:3)

EXAMPLE VIII

[0680] 2-methyl-4,5,7,8-tetrahydro-1H-imidazo[4,5-d]azepine

[0681] 3 equivalents (4.463 g) of sodium methoxide are placed in MeOH atambient temperature, 7.8 g of acetamidine-hydrochloride are added andthe mixture is stirred for 30 min. Then

[0682] 10 g of N-benzyl-5-bromohexahydro-4-azepinone are added. Afteranother 30 minutes an additioal 2 eq. (2.976 g) of sodium methoxide areadded to the mixture which is refluxed for 11 hours. After cooling toambient temperature the mixture is fully concentrated by evaporation invacuo, the material remaining is triturated with about 140 ml ofisopropanol, filtered and the filtrate is evaporated down again. Thecrude product is taken up in 50 ml of 1N K₂CO₃ solution and extracted3×with 40 ml of CH₂Cl₂. The organic phases are dried with MgSO₄,filtered off and evaporated to dryness. The residue is chromatographedover silica gel (CH₂Cl₂/MeOH=87:13 to 70:30). Yield: 1,7 g MS (M+H)+=242

[0683] 1H-NMR (D6-DMSO; 400 MHz) δ: 2.13 (s, 3H), 2.58 (t, 4H), 2.79 (t,4H), 3.72 (s, 2H), 7.20-7.40 (m, 5H), 11.11 (br s, 1H).

[0684] The N-benzylated2-methyl-4,5,7,8-tetrahydro-1H-imidazo[4,5-d]azepine is dissolved in 55ml ethanol and combined with 500 mg of palladium on charcoal (5%). Themixture is hydrogenated in a shaking autoclave at ambient temperatureunder 50 psi of pressure for 48 hours. The catalyst is then filtered offand the mixture is evaporated down in vacuo. Yield: 900 mg

[0685] MS (M+H)+=152

EXAMPLE IX

[0686] 3-pyrrolidin-1-ylmethyl-piperidine

[0687] The educt 3-(1-pyrrolidinylmethyl)-pyridine (24.6 g) is taken upin 250 ml glacial acetic acid and hydrogenated with 2 g of PtO₂ under 3bar H₂ at ambient temperature. The solution filtered off is evaporateddown, combined with ice and made alkaline with solid KOH while cooling.Afer extracting three times with 250 ml of diethylether the crudeproduct is dried with MgSO₄. After the MgSO₄ has been filtered off thesolvent is eliminated and the amine is distillled in a water jet vacuumat a boiling point of 123° C.

[0688] Yield: 17.9 g

[0689] Melting point: 47° C.

[0690] CHN analysis calculated: 71.37%/11.98%/16.65%

[0691] found: 71.00%/12.04%/16.01%

EXAMPLE X

[0692] N,N-dimethyl-2-[methyl-(2-piperidin-4-yl-ethyl)-amino]-acetamide

[0693] 4-[2-(methylamino)ethyl]pyridine (34.4 g) and 29.18 g ofchloroacetic acid-dimethylamide are dissolved in 200 ml of methanol.After the addition of 20 g of sodium bicarbonate the mixture is refluxedfor 5 hours with stirring. For working up the mixture is combined with1000 ml of tetrahydrofuran, decanted off from the precipitated salts andthe solution is filtered through active charcoal. After the liminationof the solvent,N,N-dimethyl-2-[methyl-(2-pyridine-4-yl-ethyl)-amino]-acetamide isobtained as a crude product.

[0694] Of the crudeN,N-dimethyl-2-[methyl-(2-pyridine-4-yl-ethyl)-amino]-acetamide, 44 gare dissolved in 500 ml of glacial acetic acid and hydrogenated with 4 gof PtO2 at ambient temperature under 3 bar H2. After the catalyst hasbeen removed by suction filtering the filtrate is evaporated down. Theresidue is made alkaline with 50% potassium hydroxide solution whilecooling with ice and the product obtained is taken up in ether. Theether solution is dried over sodium sulphate, filtered and the solutionis evaporated down. The product is left as a yellow oil. Yield: 42 g

EXAMPLE XI

[0695] 2-methyl-2,8-diaza-spiro[5.5]undecan-5-ol

[0696] 87 g of acrylonitrile are added dropwise at ambient temperature,with stirring, to 75 ml of Triton B and 277 g of ethyl1-methyl-4-oxo-piperidin-3-carboxylate in 1500 ml of dioxane, while thetemperature of the mixture rises to 48° C. The solution is stirred for afurther 4 hours at ambient temperature before the solvent is distilledoff in vacuo. The residue is combined with diethylether and extractedtwice with saturated saline solution. After the organic phase has beendried the solvent is distilled off. The product is distilled under ahigh vacuum.

[0697] Yield: 220.5 g.

[0698] In the autoclave 90 g of ethyl3-(2-cyano-ethyl)-1-methyl-4-oxo-piperidin-3-carboxylate arehydrogenated in 1800 ml of methanolic ammonia and 15 g of Raney nickel(3 bar). When the mxture is no longer absorbing any hydrogen thecatalyst is removed by suction filtering and the filtrate in vacuo. Theproduct is obtained after chromatography on silica gel.

[0699] Yield: 42.6 g

[0700] Of the 11-hydroxy-8-methyl-2,8-diaza-spiro[5.5]undecan-1-oneobtained, 2 g are taken up in 20 ml of absolute tetrahydrofuran; thissolution is added dropwise, with stirring, to 1 g of LiAlH4 in 50 ml ofabsolute tetrahydrofuran. The temperature rises to 36° C., whilehydrogen is given off in copious amounts. After another 3 hours atambient temperature the mixture is refluxed for 10 hours. The reactionis stopped by the addition of 2 ml of water and 2 ml 1N aqueous sodiumhydroxide solution while cooling with ice. The product is extracted withethyl acetate and the solvent is eliminated in vacuo. Then the amine isprecipitated from absolute ethanol with HCl gas, in the form of thehydrochloride. Yield 1.44 g.

[0701] Analysis: Melting point 293-295° C. decomposition

EXAMPLE XII

[0702] 2.4-dichloro-5-trimethylsilanylethynyl-pyrimidine

[0703] 66.55 g of 2,4-dichloro-5-iodo-pyrimidine is stirred for threehous in 1.2 litres of absolute THF with 70 ml of triethylamine, 4.9 g ofpalladium chloride, 13.3 g of triphenylphosphine, 4 g of copper iodideand 39.3 ml of trimethylsilylacetylene at 40° C. After the reaction hasended the solvent is eliminated in vacuo and the dark red oil remainingis subjected to fractional distillation. The product is distilled overat 0.01 Torr and 100° C.

[0704] 1H-NMR (D6-DMSO, 400 MHz) δ: 0.20 (s, 9H), 8,90 (s, 1H)

EXAMPLE XIII

[0705] 2.4-dichloro-5-methylsulphonyl-pyrimidine

[0706] The compound is prepared from 5-bromouracil by a 3-stepsynthesis. 5-thiomethyl-uracil

[0707] 126 g of 5-bromouracil are refluxed in 1.0 litres of a 21%aqueous sodium thiomethoxide solution for 5 hours. After the reactionhas ended the mixture is cooled to 10° C. and slowly adjusted to pH 7with 330 ml of conc. hydrochloric acid (temperature should not exceed30° C.). The reaction mixture is left to stand overnight at ambienttemperature, the precipitate is filtered off, washed with 300 ml of coldwater and the solid is dried (100 g; 96%) in the drying cupboard at 80°C.

[0708] Rf=0.29 (silica gel; n-butanol)

[0709] 2.4-dichloro-5-thiomethyl-pyrimidine

[0710] 100 g of 5-thiomethyluracil are added to 580 ml of phosphorusoxychloride. 80 ml of dimethylaniline are added at ambient temperatureand the reaction mixture is refluxed for 3 hours. Then the excessphosphorus oxychloride is evaporated off, the residue is poured onto 500ml of ice water and the aqueous phase is extracted three times with 400ml of diethylether. The ether extracts are washed four times with 75 mlof water, dried over sodium sulphate and evaporated down. A solid isleft, which is recrystallised twice from cyclohexane (20.0 g; 16%).

[0711] 2.4-dichloro-5-methylsulphonyl-pyrimidine

[0712] A solution of 51.2 g of 3-chloroperbenzoic acid (98%) in 450 mlof methylene chloride is added dropwise to 20.0 g of2,4-dichloro-5-thiomethyl-pyrimidine in 250 ml methylene chloride at −5°C. within 1 hour. The reaction mixture is left to thaw at ambienttemperature and stirred for 24 hours. Then the precipitate is filteredoff, the filtrate is washed successively with 50 ml of saturated sodiumsulphite solution, 50 ml of saturated sodium hydrogen carbonate solutionand 50 ml of water. The organic phase is dried over sodium sulphate andevaporated down, whereupon the product is obtained as a crystallineprecipitate anf{dot over (a)}llt (18.5 g; 80%). No further purificationis required.

[0713] Rf=0.49 (silica gel; cyclohexane/ethyl acetate=1:1)

[0714] GC/MS: (M+H)⁺=226/228 (2Cl);

[0715] 1H-NMR (D6-DMSO, 400 MHz) δ: 3.42 (s, 3H), 9.18 (s, 1H).

EXAMPLE XIV

[0716] 2,4-dichloro-5-isopropoxy-pyrimidine.

[0717] The compound is prepared from chloracetic acid and thiourea.

[0718] Methyl isopropoxyacetate

[0719] 116.5 g of the sodium salt of chloracetic acid are slowly addedat 80° C. to a sodium isopropoxide solution (freshly prepared from 23 gof sodium and 250 ml of isopropylalcohol). The reaction mixture isrefluxed for 2 hours and then combined with 500 ml of water. The mixtureis evaporated down to a total volume of 200 ml and adjusted to pH1 withconc. sulphuric acid. The precipitate formed is filtered off, the twophases of the filtrate are and the organic phase is fractionallydistilled in vacuo (101-103° C./10 Torr; 83 g; 70%). The2-isopropoxy-acetic acid thus obtained is heated together with 0.2 ml ofconc. sulphuric acid in 57 ml of methanol and 200 ml benzene for 7 hoursusing a water separator. After the excess methanol has been distilledoff the residue is fractionally distilled in vacuo (50-55° C./10 Torr;81.6 g; 88%).

[0720] 4-hydroxy-5-isopropoxy-2-mercapto-pyrimidine

[0721] 81.6 g of methyl isopropoxyacetate are added together with 50.3ml of ethylformate to a previously prepared suspension of 14.2 g ofsodium in 200 ml of toluene. The reaction mixture is left to standovernight, the toluene is decanted off and the unpurified residue of the2-isopropoxy-2-methoxycarbonyl-sodium ethoxide is used without anyfurther purification for the next step.

[0722] The complete residue is dissolved in 150 ml of ethanol withheating. Then 47.0 g of thiourea are added thereto and the reactionmixture is refluxed for 5 hours. After the solvent has been eliminatedusing the rotary evaporator the residue is taken up in 300 ml of waterand adjusted to pH 2, whereupon the desired product is obtained as aprecipitate, filtered off and dried overnight (60.8 g; 53%).

[0723] 5-isopropoxyuracil

[0724] 60.8 g of 4-hydroxy-5-isopropoxy-2-mercapto-pyrimidine arerefluxed together with 60 g of chloroacetic acid in 1.2 litres of waterfor 2.5 hours, during which time the precipitate dissolves completely.200 ml of conc. hydrochloric acid are added and the mixture is refluxedfor a further 7 hours. Then the reaction mixture is evaporated down to500 ml, whereupon the desired product is obtained as a precipitate,filtered off and dried overnight at 70° C. (28.6 g; 52%).

[0725] 2,4-dichloro-5-isopropoxy-pyrimidine

[0726] 28.6 g of 5-isopropoxyuracil are refluxed for 2 hours togetherwith 140 ml of phosphorus oxychloride and 44 ml of dimethylaniline. Thenthe excess phosphorus oxychloride is distilled off in vacuo. The residueis poured onto 300 ml of ice water, extracted twice with 250 ml ofdiethylether, washed four times with 50 ml of water and the etherextracts are dried over sodium sulphate. The solvent is eliminated usingthe rotary evaporator and the residue is fractionally distilled under ahigh vacuum (82-85° C./10⁻² Torr; 19.0 g; 55%.

[0727] Rf=0.62 (cyclohexane/ethyl acetate=1:1);

[0728] GC-MS (M+H)⁺=206/208 (2Cl);

[0729] 1H-NMR (D6-DMSO; 400 MHz) δ: 1.38 (s, 6H), 4.89 (m, 1H), 8.65 (s,1H).

EXAMPLE XV

[0730] 2,4-dichloro-5-isopropyl-pyrimidine.

[0731] 23.0 g of 5-isopropyluracil are refluxed for 4 hours togetherwith 139 ml of phosphorus oxychloride and 38.8 ml of dimethylaniline.Then the excess phosphorus oxychloride is distilled off in vacuo. Theresidue is poured onto 400 ml of ice water and extracted twice je 250 mlof diethylether, washed three times with 50 ml of water and the etherexstracts are dried over sodium sulphate. The solvent is eliminatedusing the rotary evaporator and the residue is fractionally distilledunder a high vacuum (70-78° C./10⁻² Torr; 25.6 g; 90%.

[0732] Rf=0.69 (ethyl acetate);

[0733] GC-MS (M+H)⁺=190/192 (2Cl);

[0734] 1H-NMR (D6-DMSO; 400 MHz) δ: 1.33 (s, 6H), 3.22 (m, 1H), 8.80 (s,1H).

EXAMPLE XVI

[0735] 3-phenyl-perhydro-azepin-4-one

[0736] 281 g of ethyl 4-bromobutyrate, 305 g of potassium carbonate and5.5 g of potassium iodide are added to 313 g of ethyl3-benzylamino-2-phenyl-propionate in 800 ml of methylethylketone and themixture is refluxed for 24 hours. For working up the precipitate isfiltered off, washed with acetone and the combined organic solutions areevaporated down. The residue is taken up in 1000 ml of diethylether,combined with 500 ml of 3N hydrochloric acid and the aqueous phase andthe hydrochloride extracted with oil are isolated. The ethereal phase isextracted twice with 3 N hydrochloric acid, the combined aqueous phasesare made alkaline again with concentrated aqueous ammonia and extractedtwice with ether. After the organic phase has been dried over magnesiumsulphate and evaporated in vacuo the product is obtained as a clear oil.

[0737] Yield: 314 g

[0738] 87.3 g of NaH is suspended in 1300 ml of toluene, 7.7 ml ofethanol are quickly added dropwise thereto. Within 10 minutes 199 g ofethyl 4-[benzyl-(2-ethoxycarbonyl-2-phenyl-ethyl)-amino]-butyrate in 230ml of toluene are added dropwise thereto and the mixture is refluxed forthree hours with stirring. After cooling to 40° C., 160 ml of ethanol isadded dropwise and then the mixture is poured onto 700 ml of ice-cooled6N HCl. The aqueous phase and the oily hydroichloride are separated offand the toluene phase is extracted three times with 300 ml of water. Thecombined acid phases, as well as the isolated oil, are heated to 140° C.for 90 minutes and then stirred overnight at ambient temperature. Themixture is then made alkaline with conc. aqueous ammonia, while coolingwith ice, extracted twice with diethyl ether, the organic phase is driedover magnesium sulphate and evaporated down. The product can berecrystallised from petroleum ether. Yield: 85.8 g.

[0739] 22.1 g of 1-benzyl-3-phenyl-perhydro-azepin-4-one hydrochlorideare dissolved in 250 ml of methanol and 10 ml of water and hydrogenatedwith 2.5 g of Pd/C (10%) for 3 hours under 5 bar of H₂. Then another 2.5g of catalyst are added and the hydrogenation step is repeated. Thecatalyst is filtered off and the mixture is evaporated down. The residueis recrystallised from ethanol. Yield: 8.2 g MS: [M]+ = 189 CHNClanalysis calculated 63.85%/7.14%/6.21%/15.71% found61.90%/7.13%/5.94%/16.79%

[0740] Melting point: 187° C. decomposition

EXAMPLE XVII

[0741] 3-(4-aminomethyl-cyclohexyl)-propionic Acid

[0742] 11.2 g of methyl 3-[4-(acetylamino-methyl)-phenyl]-propionate aredissolved in 130 ml of methanol and 24 ml of 8 N aqueous sodiumhydroxide solution are added with stirring. After 2 hours at ambienttemperature the mixture is neutralised with glacial acetic acid andconcentrated by evaporation. The residue is taken up in water andadjusted with 2 N aqueous hydrochloric acid to a pH value of 1-2. Thewhite precipitate formed is suction filtered and washed with water.

[0743] Yield 12.6 g

[0744] Melting point 144-147° C.

[0745] The intermediate product3-[4-(acetylamino-methyl)-phenyl]-propionic acid (12.6 g) is dissolvedin 200 ml of methanol and hydrogenated with 1.2 g of Rh/Pt catalystunder 3 bar H₂ atmosphere. After 90 minutes at ambient temperature thecatalyst is filtered off and the solution is evaporated to dryness.Yield 13 g

[0746] Melting point 91-94° C.

[0747] 13 g of 3-[4-(acetylamino-methyl)-cyclohexyl]-propionic acid areadded to 200 ml of semi-concentrated aqueous hydrochloric acid and theresulting solution is refluxed overnight. The mixture is combined withacetone, recrystallised and the precipitate is separated off. When themother liquor is concentrated step by step further fractions of thecrystallin product are isolated. The fractions are combined,recrystallised with isopropanol and then dried.

[0748] Yield: 10.9 g.

EXAMPLE XVIII

[0749] Methyl 4-1(pyridine-3-ylmethyl)-amino]-cyclohexane-carboxylate

[0750] 6.13 g of pyridine-3-aldehyde, 5.77 g of triethylamine and 9 g ofmethyl 4-amino-cyclohexanecarboxylate are mixed into 250 ml of methanol.3 g of Raney nickel are added thereto un order to hydrogenate themixture, with stirring, for about 6.5 hours at 50° C. and 3 bar. Afterthe catalyst has been eliminated by suction filtering the filtrate isevaporated down. The crude product is purified through silica gel withmethylene chloride/methanol.

[0751] Yield 4.1 g.

[0752] Melting point 47° C.

EXAMPLE 1

[0753]2-(3,4-dichlorophenylamino)-4-(2-acetylamino-ethylamino)-5-nitro-pyrimidine

[0754] 716 mg of 2-acetylamino-ethylamine in 8 ml of DMF are added to800 mg of 2-(3,4-dichlorophenylamino)-4-thiocyanato-5-nitro-pyrimidine(compound of Example 1) in 5 ml dimethylformamide (DMF) at ambienttemperature. The mixture goes into solution with a slightly exothermicreaction, and after 1.5 hours a yellowish precipitate is formed. After3.5 h 30 ml of water are added. The precipitate is suction filtered anddried. The residue is stirred with 30 ml of methylene chloride, suctionfiltered and dried.

[0755] Yield: 795 mg (88% of theory)

[0756] Melting point: 232° C.

[0757] R_(f)=0.6 (silica gel; methylene chloride:methanol=9:1)

[0758] The following compounds are obtained analogously to Example 1:

[0759] (1)2-(3,4-dichlorophenylamino)-4-(4-aminomethyl-cyclohexylmethylamino)-5-nitro-pyrimidine

[0760] Melting point: 210° C. (decomposition)

[0761] R_(f)=0.3 (silica gel; methylenechloride:methanol:conc.ammonia=9:1:0.1)

[0762] Prepared from the compound of Example I.

[0763] (2)2-(3,4-dichlorophenylamino)-4-(2-acetylamino-ethylamino)-5-cyano-pyrimidine

[0764] Melting point: 281° C.

[0765] R_(f)=0.6 (silica gel; cyclohexane:ethyl acetate:methanol=5:4:2)

[0766] Prepared from the compound (11) of Example III, carried out inDMSO under microwave irradiation (900 Watt).

[0767] (3)2-(2-naphthylamino)-4-(3-(2-oxo-pyrrolidin-1-yl)-propyl-1-amino)-5-trifluoromethyl-pyrimidine

[0768] Melting point: 142° C.

[0769] HPLC/MS (Method A): RT=6.13 min.; [M+H]⁺=430.2

[0770] R_(f)=0.5 (silica gel; cyclohexane:ethyl acetate:methanol=5:4:1)

[0771] Prepared from compound (8) of Example III, carried out in DMSO.

[0772] (4)2-(4-chlorophenylamino)-4-(1,4,6,7-tetrahydro-imidazo[4,5-c]pyridin-5-yl)-5-trifluoromethyl-pyrimidine

[0773] Melting point: 230° C.

[0774] HPLC/MS (Method A): RT=5.54 min.; [M+H]+=395.1

[0775] Prepared from compound (3) of Example III using DMF, dioxane andHünig base.

[0776] (5)2-(3-chlorophenylamino)-4-(1,4,6,7-tetrahydro-imidazo[4,5-c]pyridin-5-yl)-5-trifluoromethyl-pyrimidine

[0777] Melting point: 210° C.

[0778] HPLC/MS (Method A): RT=5.61 min.; [M+H]+=395.1

[0779] R_(f)=0.26 (silica gel; cyclohexane:ethyl acetate:methanol=5:4:1)

[0780] Prepared from compound (1) of Example III using DMSO and 2N NaOH.

[0781] (6)2-(4-(1-piperidinyl-methyl-)phenylamino)-4-(1,4,6,7-tetrahydro-imidazo[4,5-c]pyridin-5-yl)-5-trifluoromethyl-pyrimidine

[0782] Melting point: 105° C.

[0783] HPLC/MS (Method A): RT=4.75 min.; [M+H]+=458.3

[0784] R_(f)=0.21 (silica gel; methylene chloride:methanol:conc.ammonia=9:1:0.1)

[0785] Prepared from compound (10) of Example III using DMSO and 2NNaOH.

[0786] (7)2-(4-amino-3,5-dichlorophenylamino)-4-(bis-(2-hydroxy-ethyl)-amino)-5-nitro-pyrimidine

[0787] HPLC/MS (Method A): RT=5.67 min.; [M+H]+=403.1

[0788] (8)2-(4-aminosulphonyl-phenylamino)-4-(3-(2-oxo-pyrrolidin-1-yl)-propyl-1-amino)-5-nitro-pyrimidine

[0789] HPLC/MS (Method A): RT=5.4 min.; [M+H]+=436.1

[0790] (9)2-(3,4-dichlorophenylamino)-4-(3-(2-aza-bicyclo[2.2.1]hept-5-en-2-yl)-propylamino)-5-trifluoromethyl-pyrimidine

[0791] (10)2-(4-chlorophenylamino)-4-(1,4,6,7-tetrahydro-imidazo[4,5-c]pyridin-5-yl)-5-nitro-pyrimidine

[0792] HPLC/MS (Method A): RT=5.38 min.; [M+H]+=372.1

[0793] (11)2-(4-chlorophenylamino)-4-(3-(2-oxo-pyrrolidin-1-yl)-propyl-1-amino)-5-trifluoromethyl-pyrimidine

[0794] HPLC/MS (Method A): RT=6.12 min.; [M+H]+=414.1

[0795] Melting point: 260-262° C.

[0796] Rf value: 0.82 (silica gel; cyclohexane/EE/MeOH=5:4:1)

[0797] HPLC/MS (Method D): RT=5.837 min.; [M+H]+=414; Abs./max 250 nm

[0798] (12)2-(3-chlorophenylamino)-4-(3-aminopropyl-amino)-5-trifluoromethyl-pyrimidine

[0799] HPLC/MS (Method A): RT=5.13 min.; [M+H]+=346.1

[0800] (13)2-(4-carboxyphenylamino)-4-[N-(3-dimethylamino-propyl-)N-methyl]-amino-5-nitro-pyrimidine

[0801] HPLC/MS (Method A): RT=4.83 min.; [M+H]+=375.2

[0802] (14)2-(3,5-dichlorophenylamino)-4-(1,4,6,7-tetrahydro-imidazo[4,5-c]pyridin-5-yl)-5-trifluoromethyl-pyrimidine

[0803] HPLC/MS (Method A): RT=5.85 min.; [M+H]+=429.1

[0804] (15)2-(3-chloro-4-fluoro-phenylamino)-4-(1,4,6,7-tetrahydro-imidazo[4,5-c]pyridin-5-yl)-5-nitro-pyrimidine

[0805] HPLC/MS (Method A): RT=5.39 min.; [M+H]+=390.1

[0806] (16)2-(3,4-dichloro-phenylamino)-4-(2-nitrobenzylamino)-5-trifluoromethyl-pyrimidine

[0807] HPLC/MS (Method A): RT 7.77 min.; [M+H]+=458.1

[0808] (17)2-(4-carboxy-phenylamino)-4-(1,4,6,7-tetrahydro-imidazo[4,5-c]pyridin-5-yl)-5-trifluoromethyl-pyrimidine

[0809] HPLC/MS (Method A): RT=5.12 min.; [M+H]+=405.1

[0810] (18)2-(4-carboxy-phenylamino)-4-(trans-4-dimethylamino-cyclohexylamino)-5-nitro-pyrimidine

[0811] HPLC/MS (Method A): RT=4.97 min.; [M+H]+=401.2

[0812] (19)2-(4-bromo-phenylamino)-4-(1,4,6,7-tetrahydro-imidazo[4,5-c]pyridin-5-yl)-5-trifluoromethyl-pyrimidine

[0813] HPLC/MS (Method A): RT=5.61 min.; [M+H]+=439.1

[0814] (20)2-(3,5-dichloro-phenylamino)-4-(3-amino-cyclohexylamino)-5-trifluoromethyl-pyrimidine

[0815] HPLC/MS (Method A): RT=5.71 min.; [M+H]+=420.1

[0816] (21)2-(4-carboxy-phenylamino)-4-(3-(2-oxo-pyrrolidin-1-yl)-propyl-1-amino)-5-trifluoromethyl-pyrimidine

[0817] HPLC/MS (Method A): RT=5.44 min.; [M+H]+=424.2

[0818] (22)2-(3-aminocarbonyl-phenylamino)-4-(1,4,6,7-tetrahydro-imidazo[4,5-c]pyridin-5-yl)-5-nitro-pyrimidine

[0819] HPLC/MS (Method A): RT=4.71 min.; [M+H]+=381.2

[0820] (23)2-(4-(2-carboxy-1-ethyl-)phenylamino)-4-(1,4,6,7-tetrahydro-imidazo[4,5-c]pyridin-5-yl)-5-trifluoromethyl-pyrimidine

[0821] HPLC/MS (Method A): RT=5.13 min.; [M+H]+=433.2

[0822] (24)2-(3-bromo-phenylamino)-4-(3-amino-propylamino)-5-trifluoromethyl-pyrimidine

[0823] HPLC/MS (Method A): RT=5.16 min.; [M+H]+390.1

[0824] (25)2-(3,4-dichloro-phenylamino)-4-(2-aminocarbonyl-1-ethylamino)-5-trifluoromethyl-pyrimidine

[0825] HPLC/MS (Method A): RT=6.36 min.; [M+H]+=394.1

[0826] (26)2-(4-phenylaminocarbonyl-phenylamino)-4-(1,4,6,7-tetrahydro-imidazo[4,5-c]pyridin-5-yl)-5-nitro-pyrimidine

[0827] HPLC/MS (Method A): RT=5.3 min.; [M+H]+=457.2

[0828] (27)2-(4-nitro-phenylamino)-4-(1,4,6,7-tetrahydro-imidazo[4,5-c]pyridin-5-yl)-5-nitro-pyrimidine

[0829] HPLC/MS (Method A): RT=5.21 min.; [M+H]+=383.2

[0830] (28)2-(4-chloro-phenylamino)-4-(3-(4-(pyrrolidin-1-yl)butyl)-piperidin-1-yl)-5-nitro-pyrimidine

[0831] HPLC/MS (Method A): RT=5.89 min.; [M+H]+=459.2

[0832] (29)2-(4-carboxy-phenylamino)-4-(1,4,6,7-tetrahydro-imidazo[4,5-c]pyridin-5-yl)-5-nitro-pyrimidine

[0833] HPLC/MS (Method A): RT=4.85 min.; [M+H]+=382.1

[0834] (30)2-(3,4-dichloro-phenylamino)-4-(1-methyl-piperidin-4-yl-methylamino)-5-trifluoromethyl-pyrimidine

[0835] HPLC/MS (Method A): RT=5.58 min.; [M+H]+=434.1

[0836] (31)2-phenylamino-4-(3-(2-oxo-pyrrolidin-1-yl)-propyl-1-amino)-5-trifluoromethyl-pyrimidine

[0837] HPLC/MS (Method A): RT=5.36 min.; [M+H]+=380.2

[0838] (32)2-(4-cyano-phenylamino)-4-(1,4,6,7-tetrahydro-imidazo[4,5-c]pyridin-5-yl)-5-nitro-pyrimidine

[0839] HPLC/MS (Method A): RT=5.11 min.; [M+H]+=363.1

[0840] (33)2-phenylamino-4-(4-aminomethyl-cyclohexylmethylamino)-5-trifluoromethyl-pyrimidine

[0841] HPLC/MS (Method A): RT=4.93 min.; [M+H]+=380.2

[0842] (34)2-(4-chloro-phenylamino)-4-(3-amino-cyclohexylamino)-5-nitro-pyrimidine

[0843] HPLC/MS (Method A): RT=5.41 min.; [M+H]+=363.1

[0844] (35)2-(3,4-dichloro-phenylamino)-4-(3-amino-propylamino)-5-trifluoromethyl-pyrimidine

[0845] HPLC/MS (Method A): RT=5.45 min.; [M+H]+=380.1

[0846] (36)2-(4-chloro-phenylamino)-4-(3-amino-propylamino)-5-trifluoromethyl-pyrimidine

[0847] HPLC/MS (Method A): RT=5.02 min.; [M+H]+=346.1

[0848] (37)2-(3,4-dichloro-phenylamino)-4-(cis-4-hydroxy-cyclohexylamino)-5-trifluoromethyl-pyrimidine

[0849] HPLC/MS (Method A): RT=6.84 min.; [M+H]+=421.1

[0850] (38)2-(3-bromo-phenylamino)-4-(1,4,6,7-tetrahydro-imidazo[4,5-c]pyridin-5-yl)-5-trifluoromethyl-pyrimidine

[0851] HPLC/MS (Method A): RT=5.6 min.; [M+H]+=439.1

[0852] (39)2-(2-naphthylamino)-4-(3-amino-cyclohexylamino)-5-trifluoromethyl-pyrimidine

[0853] HPLC/MS (Method A): RT=5.34 min.; [M+H]+=402.2

[0854] (40)2-(3,4-dichloro-phenylamino)-4-(3-acetylaminomethyl-piperidin-1-yl)-5-trifluoromethyl-pyrimidine

[0855] HPLC/MS (Method A): RT=7.12 min.; [M+H]+=462.1

[0856] (41)2-(3,4-dichloro-phenylamino)-4-(3-(2-oxo-pyrrolidin-1-yl)-propyl-1-amino)-5-trifluoromethyl-pyrimidine

[0857] HPLC/MS (Method A): RT=6.85 min.; [M+H]+=448.1D

[0858] (42)2-(3-bromo-phenylamino)-4-(4-aminomethyl-piperidin-1-yl)-5-nitro-pyrimidine

[0859] HPLC/MS (Method A): RT=5.36 min.; [M+H]+=407.1

[0860] (43)2-(4-bromo-phenylamino)-4-(4-aminomethyl-piperidin-1-yl)-5-nitro-pyrimidine

[0861] HPLC/MS (Method A): RT=5.53 min.; [M+H]+=430.1

[0862] (44)2-(4-chloro-phenylamino)-4-(N-(1-methyl-piperidin-4-yl)-N-methyl-amino)-5-nitro-pyrimidine

[0863] HPLC/MS (Method A): RT=5.32 min.; [M+H]+=377.2

[0864] (45)2-(3,4-dichloro-phenylamino)-4-(5-hydroxy-1-pentylamino)-5-trifluoromethyl-pyrimidine

[0865] HPLC/MS (Method A): RT=6.79 min.; [M+H]+=409.1

[0866] (46)2-(4-(2-carboxy-1-ethyl)-phenylamino)-4-(2-(3-hydroxyphenyl)-1-ethyl-amino)-5-trifluoromethyl-pyrimidine

[0867] HPLC/MS (Method A): RT=5.64 min.; [M+H]+=447.1

[0868] (47)2-(3-bromo-phenylamino)-4-(3-(2-oxo-pyrrolidin-1-yl)-propyl-1-amino)-5-trifluoromethyl-pyrimidine

[0869] HPLC/MS (Method A): RT=6.37 min.; [M+H]+=458.1D

[0870] (48)2-(4-chloro-phenylamino)-4-((1S)-1-carboxy-1-ethylamino)-5-nitro-pyrimidine

[0871] HPLC/MS (Method B): RT=2,5 min.; [M+H]+=338

[0872] (49)2-(3,5-dichloro-phenylamino)-4-(3-(2-oxo-pyrrolidin-1-yl)-propyl-1-amino)-5-trifluoromethyl-pyrimidine

[0873] HPLC/MS (Method A): RT=7.15 min.; [M+H]+=448.1

[0874] (50)2-(3-nitro-phenylamino)-4-(3-hydroxymethyl-piperidin-1-yl)-5-nitro-pyrimidine

[0875] HPLC/MS (Method A): RT=6.39 min.; [M+H]+=375.2

[0876] (51)2-(4-bromo-phenylamino)-4-(3-amino-propylamino)-5-trifluoromethyl-pyrimidine

[0877] HPLC/MS (Method A): RT=5.12 min.; [M+H]+=390.1

[0878] (52)2-(4-chloro-phenylamino)-4-(4-(N-acetyl-N-methyl-aminomethyl)-piperidin-1-yl)-5-nitro-pyrimidine

[0879] HPLC/MS (Method A): RT=6.61 min.; [M+H]+=419.2

[0880] (53)2-(3,4-dichloro-phenylamino)-4-(2-(4-hydroxy-3-methoxy-phenyl)-2-hydroxy-1-ethylamino)-5-trifluoromethyl-pyrimidine

[0881] HPLC/MS (Method A): RT=6.79 min.; [M+H]+=489.1

[0882] (54)2-(4-carboxy-phenylamino)-4-(trans-4-dimethylamino-cyclohexylamino)-5-trifluoromethyl-pyrimidine

[0883] HPLC/MS (Method A): RT=4.93 min.; [M+H]+=424.2

[0884] (55)2-(4-chloro-phenylamino)-4-((2S)-2-hydroxymethyl-pyrrolidin-1-yl)-5-nitro-pyrimidine

[0885] HPLC/MS (Method A): RT=6.59 min.; [M+H]+=350.1

[0886] Prepared using L-prolinol.

[0887] (56)2-(4-bromo-phenylamino)-4-(3-(2-oxo-pyrrolidin-1-yl)-propyl-1-amino)-5-trifluoromethyl-pyrimidine

[0888] HPLC/MS (Method A): RT=6.19 min.; [M+H]+=458.1

[0889] (57)2-(3,4-dichloro-phenylamino)-4-(3-amino-cyclohexylamino)-5-trifluoromethyl-pyrimidine

[0890] HPLC/MS (Method A): RT=5.66 min.; [M+H]+=420.1

[0891] (58)2-(3,4-dichloro-phenylamino)-4-(3-(isopropylamino)-1-propylamino)-5-trifluoromethyl-pyrimidine

[0892] HPLC/MS (Method A): RT=5.66 min.; [M+H]+=422.1

[0893] (59)2-(4-chloro-phenylamino)-4-(2-(3-hydroxy-phenyl)-2-hydroxy-1-ethylamino)-5-nitro-pyrimidine

[0894] HPLC/MS (Method A): RT=6.49 min.; [M+H]+=402.1

[0895] (60)2-(3,4-dichloro-phenylamino)-4-(1,4,6,7-tetrahydro-imidazo[4,5-c]pyridin-5-yl)-5-trifluoromethyl-pyrimidine

[0896] HPLC/MS (Method A): RT=5.78 min.; [M+H]+=429.1

[0897] (61)2-(3,4-dichloro-phenylamino)-4-(trans-4-carboxy-cyclohexylamino)-5-trifluoromethyl-pyrimidine

[0898] HPLC/MS (Method A): RT=6.99 min.; [M+H]+=449.1

[0899] (62)2-(3,4-dichloro-phenylamino)-4-(1,1-dimethyl-2-hydroxy-1-ethylamino)-5-trifluoromethyl-pyrimidine

[0900] HPLC/MS (Method A): RT=7.34 min.; [M+H]+=395.1

[0901] (63)2-(3,4-dichloro-phenylamino)-4-(5-amino-pentylamino)-5-trifluoromethyl-pyrimidine

[0902] HPLC/MS (Method A): RT=5.57 min.; [M+H]+=408.1

[0903] (64)2-(4-amino-3,5-dichlorophenylamino)-4-(3-hydroxymethyl-piperidin-1-yl)-5-nitro-pyrimidine

[0904] HPLC/MS (Method A): RT=6.43 min.; [M+H]+=413.1

[0905] (65)2-(3,4-dichloro-phenylamino)-4-(6-hydroxy-1-hexylamino)-5-trifluoromethyl-pyrimidine

[0906] HPLC/MS (Method A): RT=7.06 min.; [M+H]+=423.1

[0907] (66)2-(3,4-dichloro-phenylamino)-4-((1S)-1-carboxy-2-(1H-imidazol-4-yl)-ethylamino)-5-trifluoromethyl-pyrimidine

[0908] HPLC/MS (Method A): RT=5.51 min.; [M+H]+=461.1

[0909] Prepared using L-histidine.

[0910] (67)2-(3-chloro-phenylamino)-4-(3-(2-oxo-pyrrolidin-1-yl)-propyl-1-amino)-5-trifluoromethyl-pyrimidine

[0911] HPLC/MS (Method A): RT=6.24 min.; [M+H]+=414.2

[0912] (68)2-(3,4-dichlorophenylamino)-4-(2-(1H-imidazol-4-yl)-ethylamino)-5-trifluoromethyl-pyrimidine

[0913] HPLC/MS (Method A): RT=5.55 min.; [M+H]+=417.1

[0914] (69)2-(3,4-dichloro-phenylamino)-4-(4-hydroxy-but-1-ylamino)-5-trifluoromethyl-pyrimidine

[0915] HPLC/MS (Method A): RT=6.66 min.; [M+H]+=395.1

[0916] (70)2-(4-aminosulphonyl-phenylamino)-4-(4-aminomethyl-piperidin-1-yl)-5-nitro-pyrimidine

[0917] HPLC/MS (Method A): RT=4.66 min.; [M+H]+=408.2

[0918] (71)2-(3,4-dichloro-phenylamino)-4-(4-carboxy-1-butylamino)-5-trifluoromethyl-pyrimidine

[0919] HPLC/MS (Method A): RT=6.78 min.; [M+H]+=423.1

[0920] (72)2-(3,4-dichloro-phenylamino)-4-(1-methyl-4-piperidinyl-amino)-5-trifluoromethyl-pyrimidine

[0921] HPLC/MS (Method A): RT=5.58 min.; [M+H]+=420.1

[0922] (73)2-(3,4-dichloro-phenylamino)-4-(3-(3-aminopropoxy-1-propylamino)-5-trifluoromethyl-pyrimidine

[0923] HPLC/MS (Method A): RT=5.65 min.; [M+H]+=438.1

[0924] (74)2-(4-carboxy-phenylamino)-4-(1-hydroxy-2-propylamino)-5-nitro-pyrimidine

[0925] HPLC/MS (Method A): RT=5.55 min.; [M+H]+=334.1

[0926] (75)2-(4-aminosulphonyl-phenylamino)-4-(4-aminomethyl-cyclohexylmethylamino)-5-nitro-pyrimidine

[0927] HPLC/MS (Method A): RT=4.93 min.; [M+H]+=436.2

[0928] (76)2-(3,4-dichloro-phenylamino)-4-(2-(3-hydroxy-phenyl)-2-hydroxy-1-ethylamino)-5-trifluoromethyl-pyrimidine

[0929] HPLC/MS (Method A): RT=6.85 min.; [M+H]+=459.1

[0930] (77)2-(3-chloro-phenylamino)-4-(5-amino-1-pentylamino)-5-trifluoromethyl-pyrimidine

[0931] HPLC/MS (Method A): RT=5.19 min.; [M+H]+=374.1

[0932] (78)2-(3,4-dichlorophenylamino)-4-(4-nitrobenzylamino)-5-trifluoromethyl-

[0933] HPLC/MS (Method A): RT=7.72 min.; [M+H]+=458.1

[0934] (79)2-(4-chloro-phenylamino)-4-(5-amino-pentyl-1-amino)-5-trifluoromethyl-pyrimidine

[0935] HPLC/MS (Method A): RT=5.12 min.; [M+H]+=374.1

[0936] (80)2-(3,4-dichloro-phenylamino)-4-(2-amino-1-ethylamino)-5-trifluoromethyl-pyrimidine

[0937] 100 mg of(4-chloro-5-trifluoromethyl-pyrimidin-2-yl)-(3,4-dichloro-phenyl)-amine,tert-butyl (2-amino-ethyl)-carbaminate (1 eq.) and diisopropylethylamine(2 eq.) were stirred in 2 ml of isopropanol for several hours at ambienttemperature. The reaction mixture was mixed with 2 ml of saturatedNaHCO3 solution and extracted with ethyl acetate. The organic phase wasdried over MgSO4 and evaporated down. The crude product was washed withdiethyl ether and dichloromethane and purified by chromatography(CH2Cl2/MeOH gradient, silica gel). The product was then treated withTFA/CH₂Cl2 (1:1), mixed with NaHCO3, extracted with ethyl acetate, driedover MgSO4 and evaporated down.HPLC/MS (Method A): RT=5.54 min.;[M+H]+=366.1

[0938] Melting point: 115-117° C.

[0939] R_(f)=0,13 (silica gel; methylene chloride:methanol=4:1)

[0940] HPLC/MS (Method F): RT=3,84 min.; [M+H]+=367; Abs. λ max=258,9 nm

[0941] (81)2-(3,4-dichloro-phenylamino)-4-(4-dimethylaminomethyl-cyclohexylmethylamino)-5-trifluoromethyl-pyrimidine

[0942] HPLC/MS (Method A): RT=5.78 min.; [M+H]+=476.2

[0943] (82)2-(4-chloro-phenylamino)-4-(N-methyl-N-(2-cyano-1-ethyl)-amino)-5-nitro-pyrimidine

[0944] HPLC/MS (Method A): RT=6.74 min.; [M+H]+=333.1

[0945] (83)2-(4-chloro-phenylamino)-4-(3-acetylaminomethyl-piperidin-1-yl)-5-nitro-pyrimidine

[0946] HPLC/MS (Method A): RT=6.46 min.; [M+H]+=405.2

[0947] (84)2-(4-carboxy-phenylamino)-4-(4-(2-pyridyl)-piperazin-1-yl)-5-nitro-pyrimidine

[0948] HPLC/MS (Method A): RT=5.04 min.; [M+H]+=422.2

[0949] (85)2-(3,4-dichloro-phenylamino)-4-(2-(1-methyl-2-pyrrolidinyl)-1-ethylamino)-5-trifluoromethyl-pyrimidineR_(f)=0,16 (silica gel; methylene chloride:methanol=9:1)

[0950] HPLC/MS (Method G): RT=3.66 min.; [M+H]+=435; Abs./max 266.5 nm

[0951] (86)2-(4-chloro-phenylamino)-4-(4-carboxy-1-butylamino)-5-nitro-pyrimidine

[0952] HPLC/MS (Method A): RT=6.55 min.; [M+H]+=366.1

[0953] (87)2-(3,4-dichloro-phenylamino)-4-(bis-(2-hydroxy-ethyl)-amino)-5-trifluoromethyl-pyrimidine

[0954] HPLC/MS (Method A): RT=6.4 min.; [M+H]+=411.1

[0955] (88)2-(3-bromo-phenylamino)-4-(4-aminomethyl-cyclohexylmethylamino)-5-trifluoromethyl-

[0956] HPLC/MS (Method A): RT=5.46 min.; [M+H]+=458.1

[0957] (89)2-(3,4-dichloro-phenylamino)-4-(2-(4-hydroxy-phenyl)-2-hydroxy-1-ethylamino)-5-trifluoromethyl-pyrimidine

[0958] HPLC/MS (Method A): RT=6.73 min.; [M+H]+=459.1

[0959] (90)2-(3,4-dichloro-phenylamino)-4-(4-aminomethyl-piperidin-1-yl)-5-trifluoromethyl-pyrimidine

[0960] HPLC/MS (Method A): RT=5.78 min.; [M+H]+=420.1

[0961] (91)2-(4-aminocarbonyl-phenylamino)-4-(2-(3-hydroxypropyl)-piperidin-1-yl)-5-nitro-pyrimidine

[0962] HPLC/MS (Method A): RT=5.65 min.; [M+H]+=401.2

[0963] (92)2-(3-nitro-phenylamino)-4-(4-aminomethyl-cyclohexylmethylamino)-5-nitro-pyrimidine

[0964] HPLC/MS (Method A): RT=5.41 min.; [M+H]+=402.2

[0965] (93)2-(3,4-dichloro-phenylamino)-4-(2-methoxy-1-ethylamino)-5-trifluoromethyl-pyrimidine

[0966] HPLC/MS (Method A): RT=7.37 min.; [M+H]+=381.1

[0967] (94)2-(4-methoxycarbonyl-phenylamino)-4-(4-aminomethyl-cyclohexylmethylamino)-5-nitro-pyrimidine

[0968] HPLC/MS (Method A): RT=5.37 min.; [M+H]+=415.2

[0969] (95)2-(4-chloro-phenylamino)-4-(3-(2-oxo-pyrrolidin-1-yl)-propyl-1-amino)-5-nitro-pyrimidine

[0970] HPLC/MS (Method A): RT=6.43 min.; [M+H]+=391.2

[0971] (96)2-(3,4-dichloro-phenylamino)-4-(3-hydroxymethyl-piperidin-1-yl)-5-trifluoromethyl-pyrimidine

[0972] HPLC/MS (Method A): RT=7.42 min.; [M+H]+=421.1

[0973] (97)2-(3-cyano-phenylamino)-4-(1,4,6,7-tetrahydro-imidazo[4,5-c]pyridin-5-yl)-5-nitro-pyrimidine

[0974] HPLC/MS (Method A): RT=5.12 min.; [M+H]+=363.2

[0975] (98)2-(4-benzylaminocarbonyl-phenylamino)-4-(4-aminomethyl-cyclohexylmethylamino)-5-nitro-pyrimidine

[0976] HPLC/MS (Method A): RT=5.45 min.; [M+H]+=490.3

[0977] (99)2-(3,4-dichloro-phenylamino)-4-(2-(4-(2-hydroxyethyl)-piperazin-1-yl)-1-ethylamino))-5-trifluoromethyl-pyrimidine

[0978] HPLC/MS (Method A): RT=5.42 min.; [M+H]+=479.2

[0979] (100)2-(4-amino-3,5-dichlorophenylamino)-4-(4-aminomethyl-cyclohexylmethylamino)-5-nitro-pyrimidine

[0980] HPLC/MS (Method A): RT=5.44 min.; [M+H]+=440.2

[0981] (101)2-(4-aminocarbonyl-phenylamino)-4-(3-hydroxymethyl-piperidin-1-yl)-5-nitro-pyrimidine

[0982] HPLC/MS (Method A): RT 5.44 min.; [M+H]+=373.2

[0983] (102)2-(3,4-dichloro-phenylamino)-4-(2-(3-hydroxyphenyl)-1-ethylamino)-5-trifluoromethyl-pyrimidine

[0984] HPLC/MS (Method A): RT=7.32 min.; [M+H]+=443.1

[0985] (103)2-(3,4-dichloro-phenylamino)-4-(3-hydroxy-piperidin-1-yl)-5-trifluoromethyl-pyrimidine

[0986] HPLC/MS (Method A): RT=7.31 min.; [M+H]+=407.1

[0987] (104)2-(3,4-dichloro-phenylamino)-4-(2-morpholino-1-ethylamino)-5-trifluoromethyl-pyrimidine

[0988] (105)2-(4-bromo-phenylamino)-4-(4-aminomethyl-cyclohexylmethylamino)-5-trifluoromethyl-pyrimidine

[0989] HPLC/MS (Method A): RT=5.42 min.; [M+H]+=458.1

[0990] (106)2-(4-chloro-phenylamino)-4-(5-aminopentylamino)-5-nitro-pyrimidine

[0991] HPLC/MS (Method A): RT=5.41 min.; [M+H]+=351.1

[0992] (107)2-(4-chloro-phenylamino)-4-(4-aminomethyl-cyclohexylmethylamino)-5-trifluoromethyl-pyrimidine

[0993] HPLC/MS (Method A): RT=5.33 min.; [M+H]+=414.2

[0994] (108)2-(3-nitro-phenylamino)-4-(2-(3-hydroxypropyl)-piperidin-1-yl)-5-nitro-pyrimidine

[0995] HPLC/MS (Method A): RT=6.68 min.; [M+H]+=403.2

[0996] (109)2-(3,4-dichlorophenylamino)-4-(4-amino-cyclohexylamino)-5-trifluoromethyl-pyrimidine

[0997] HPLC/MS (Method A): RT=5.55 min.; [M+H]+=420.1

[0998] (110)2-(4-chloro-phenylamino)-4-(2-methoxy-1-ethylamino)-5-nitro-pyrimidine

[0999] Melting point: 153-155° C.

[1000] (111)2-(4-carboxyphenylamino)-4-(4-amino-cyclohexylamino)-5-trifluoromethyl-pyrimidine

[1001] HPLC/MS (Method A): RT=4.93 min.; [M+H]+=396.2

[1002] (112)2-(4-(2-carboxy-1-ethyl)-phenylamino)-4-(1,4,6,7-tetrahydro-imidazo[4,5-c]pyridin-5-yl)-5-nitro-pyrimidine

[1003] HPLC/MS (Method A): RT=4.98 min.; [M+H]+=410.2

[1004] (113)2-(4-amino-3,5-dichlorophenylamino)-4-(1,4,6,7-tetrahydro-imidazo[4,5-c]pyridin-5-yl)-5-nitro-pyrimidine

[1005] HPLC/MS (Method A): RT=5.24 min.; [M+H]+=421.1

[1006] (114)2-(4-aminocarbonyl-phenylamino)-4-(1,4,6,7-tetrahydro-imidazo[4,5-c]pyridin-5-yl)-5-nitro-pyrimidine

[1007] HPLC/MS (Method A): RT=4.67 min.; [M+H]+=381.2

[1008] (115)2-(4-chloro-3-methyl-phenylamino)-4-(4-aminomethyl-cyclohexylmethylamino)-5-nitro-pyrimidine

[1009] HPLC/MS (Method A): RT=5.66 min.; [M+H]+=405.2

[1010] (116)2-(4-bromophenylamino)-4-(1,4,6,7-tetrahydro-imidazo[4,5-c]pyridin-5-yl)-5-nitro-pyrimidine

[1011] HPLC/MS (Method A): RT=5.41 min.; [M+H]+=416.1

[1012] (117)2-(3,4-dichlorophenylamino)-4-(7-methyl-2,7-diaza-spiro[4.4]non-2-yl)-5-trifluoromethyl-pyrimidine

[1013] (118)2-phenylamino-4-(1,4,6,7-tetrahydro-imidazo[4,5-c]pyridin-5-yl)-5-trifluoromethyl-pyrimidine

[1014] HPLC/MS (Method A): RT=5.23 min.; [M+H]+=361.2

[1015] (119)2-(3-bromophenylamino)-4-(1,4,6,7-tetrahydro-imidazo[4,5-c]pyridin-5-yl)-5-nitro-pyrimidine

[1016] HPLC/MS (Method A): RT=5.4 min.; [M+H]+=416.1

[1017] (120)2-(3,4-dichlorophenylamino)-4-(4-dimethylamino-cyclohexylamino)-5-trifluoromethyl-pyrimidine

[1018] HPLC/MS (Method A): RT=5.62 min.; [M+H]+=448.1

[1019] (121)2-(3,4-dichlorophenylamino)-4-(2-(imidazol-1-yl)-1-ethylamino)-5-trifluoromethyl-pyrimidine

[1020] HPLC/MS (Method A): RT=5.63 min.; [M+H]+=417.1

[1021] (122)2-(3-nitro-phenylamino)-4-(1,4,6,7-tetrahydro-imidazo[4,5-c]pyridin-5-yl)-5-nitro-pyrimidine

[1022] HPLC/MS (Method A): RT=5.2 min.; [M+H]+=383.1

[1023] (123)2-(4-chloro-phenylamino)-4-(N-(2-hydroxybenzyl)-N-methyl-amino)-5-nitro-pyrimidine

[1024] HPLC/MS (Method A): RT=7.07 min.; [M+H]+=386.1

[1025] (124)2-(4-phenylaminocarbonyl-phenylamino)-4-(4-aminomethyl-cyclohexylmethylamino)-5-nitro-pyrimidine

[1026] HPLC/MS (Method A): RT=5.5 min.; [M+H]+=476.3

[1027] (125)2-(4-fluoro-phenylamino)-4-(1,4,6,7-tetrahydro-imidazo[4,5-c]pyridin-5-yl)-5-nitro-pyrimidine

[1028] HPLC/MS (Method A): RT=5.13 min.; [M+H]+=356.1

[1029] (126)2-(3,4-dichlorophenylamino)-4-(3-(3-hydroxy-8-methyl-8-aza-bicyclo[3.2.1]octyl)-methylamino)-5-trifluoromethyl-pyrimidine

[1030] HPLC/MS (Method A): RT=5.61 min.; [M+H]+=476.1

[1031] (127)2-(4-carboxy-phenylamino)-4-(4-ethoxycarbonyl-piperidin-1-yl)-5-nitro-pyrimidine

[1032] HPLC/MS (Method A): RT=6.37 min.; [M+H]+=416.2

[1033] (128)2-(3,4-dichlorophenylamino)-4-(trans-4-hydroxy-cyclohexylamino)-5-trifluoromethyl-

[1034] HPLC/MS (Method A): RT=6.87 min.; [M+H]+=421.1

[1035] (129)2-(3,4-dichlorophenylamino)-4-(2-(1H-pyrazol-4-yl)-1-ethylamino)-5-trifluoromethyl-pyrimidine

[1036] (130) 2-(phenylamino)-4-(˜1methyl-piperidin-4-yl-methylamino)-5-trifluoromethyl-pyrimidine

[1037] HPLC/MS (Method A): RT=4.68 min.; [M+H]+=352.2

[1038] (131)2-(4-chloro-phenylamino)-4-(1-methyl-piperidin-4-yl-methylamino)-5-trifluoromethyl-pyrimidine

[1039] HPLC/MS (Method A): RT=5.23 min.; [M+H]+=386.2

[1040] (132)2-(4-bromo-phenylamino)-4-(1-methyl-piperidin-4-yl-methylamino)-5-trifluoromethyl-pyrimidine

[1041] HPLC/MS (Method A): RT=5.32 min.; [M+H]+=430.1D

[1042] (133)2-(3-bromo-phenylamino)-4-(1-methyl-piperidin-4-yl-methylamino)-5-trifluoromethyl-pyrimidine

[1043] HPLC/MS (Method A): RT=5.39 min.; [M+H]+=430.1

[1044] (134)2-(3-chloro-phenylamino)-4-(4-aminomethyl-piperidin-1-yl)-5-trifluoromethyl-pyrimidine

[1045] HPLC/MS (Method A): RT=5.50 min.; [M+H]+=386.2

[1046] (135)2-(phenylamino)-4-(4-aminomethyl-piperidin-1-yl)-5-trifluoromethyl-pyrimidine

[1047] HPLC/MS (Method A): RT=5.05 min.; [M+H]+=352.2

[1048] (136)2-(4-chloro-phenylamino)-4-(4-aminomethyl-piperidin-1-yl)-5-trifluoromethyl-pyrimidine

[1049] HPLC/MS (Method A): RT=5.45 min.; [M+H]+=386.1

[1050] (137)2-(3-bromo-phenylamino)-4-(4-aminomethyl-piperidin-1-yl)-5-trifluoromethyl-pyrimidine

[1051] HPLC/MS (Method A): RT=5.54 min.; [M+H]+=430.1

[1052] (138)2-(3-chloro-phenylamino)-4-(4-aminomethyl-cyclohexylmethylamino)-5-trifluoromethyl-pyrimidine

[1053] HPLC/MS (Method A): RT=5.40 min.; [M+H]+=414.2

[1054] (139)2-(3-chloro-phenylamino)-4-(2-amino-cyclohexylamino)-5-trifluoromethyl-pyrimidine

[1055] HPLC/MS (Method A): RT=5.63 min.; [M+H]+=386.2

[1056] (140)2-(4-chlorophenylamino)-4-(2-amino-1-ethylamino)-5-nitro-pyrimidine

[1057] Rf value: 0,30 (silica gel; methylene chloride/methanol/conc.aqueous ammonia=9:1:0.1)

[1058] (141)2-(4-chlorophenylamino)-4-[2-(acetylamino)-1-ethylamino]-5-nitro-pyrimidine

[1059] Prepared from compound 140 of Example 1 by subsequent reactionwith acetic anhydride/triethylamine.

[1060] Melting point: 224-226° C.

[1061] (142)2-(4-chlorophenylamino)-4-[4-(dimethylamino)butylamino]-5-nitro-pyrimidineMelting point: 131-132° C.

[1062] (143)2-(3,4-dichlorophenylamino)-4-(1-carboxy-1-ethylamino)-5-trifluoromethyl-pyrimidine

[1063] HPLC/MS (Method A): RT=7.04 min.; [M+H]+=395.0

[1064] (144)2-(4-carboxy-phenylamino)-4-[N-(2-hydroxyethyl)-N-benzylamino]-5-nitro-pyrimidine

[1065] HPLC/MS (Method A): RT=6.05 min.; [M+H]+=410.2

[1066] (145)2-(3,4-dichlorophenylamino)-4-((1R)-1-carboxy-2-(1H-imidazol-4-yl)-1-ethylamino)-5-trifluoromethyl-pyrimidine

[1067] HPLC/MS (Method A): RT=5.51 min.; [M+H]+=461.0

[1068] Prepared using D-histidine.

[1069] (146)2-(3,4-dichlorophenylamino)-4-(3-hydroxy-1,3-dihydro-2-oxo-indol-3-yl-methylamino)-5-trifluoromethyl-pyrimidine

[1070] HPLC/MS (Method A): RT=6.83 min.; [M+H]+=484.1

[1071] (147)2-(3,4-dichlorophenylamino)-4-(4-(2-carboxy-1-ethyl)-cyclohexylamino)-5-trifluoromethyl-

[1072] HPLC/MS (Method A): RT=7.42 min.; [M+H]+=477.1

[1073] (148)2-(4-chlorophenylamino)-4-(trans-4-carboxy-cyclohexylamino)-5-nitro-pyrimidine

[1074] HPLC/MS (Method A): RT=6.86 min.; [M+H]+=392.1

[1075] (149)2-(4-chloro-phenylamino)-4-((2R)-2-hydroxymethyl-pyrrolidin-1-yl)-5-nitro-pyrimidine

[1076] HPLC/MS (Method A): RT=6.59 min.; [M+H]+350.1

[1077] Prepared using D-prolinol.

[1078] (150)2-(4-carboxy-phenylamino)-4-(3-(2-oxo-pyrrolidin-1-yl)-propyl-1-amino)-5-nitro-pyrimidine

[1079] HPLC/MS (Method A): RT=5.57 min.; [M+H]+=401.1

[1080] (151)2-(4-chloro-phenylamino)-4-(2-morpholino-1-ethylamino)-5-nitro-pyrimidineHPLC/MS (Method B): RT=2.16 min.; [M+H]+=379.1

[1081] (152)2-(2-naphthylamino)-4-(1,4,6,7-tetrahydro-imidazo[4,5-c]pyridin-5-yl)-5-trifluoromethyl-pyrimidine

[1082] HPLC/MS (Method A): RT=5.66 min.; [M+H]+=411.2

[1083] (153)2-(4-chloro-phenylamino)-4-(2-(1H-imidazol-4-yl)-ethylamino)-5-nitro-pyrimidineHPLC/MS (Method B): RT=2.21 min.; [M+H]+=360.1

[1084] (154)2-(4-chloro-phenylamino)-4-(2-(4-hydroxy-phenyl)-2-hydroxy-1-ethylamino)-5-nitro-pyrimidine

[1085] HPLC/MS (Method B): RT=2.81 min.; [M+H]+=402.1

[1086] (155)2-(4-chloro-phenylamino)-4-(2-(4-hydroxy-3-methoxy-phenyl)-2-hydroxy-1-ethylamino)-5-nitro-pyrimidine

[1087] HPLC/MS (Method B): RT=2.68 min.; [M+H]+=432,2

[1088] (156)2-(4-chloro-phenylamino)-4-(2-(1-methyl-2-pyrrolidinyl)-1-ethylamino)-5-nitro-pyrimidine

[1089] HPLC/MS (Method B): RT=2,29 min.; [M+H]+=377,2

[1090] (157)2-(4-chloro-phenylamino)-4-(4-hydroxy-butylamino)-5-nitro-pyrimidine

[1091] Melting point: 178-182° C.

[1092] (158)2-(4-chloro-phenylamino)-4-(6-hydroxy-1-hexylamino)-5-nitro-pyrimidine

[1093] HPLC/MS (Method B): RT=2,96 min.; [M+H]+=366,2

[1094] (159)2-(4-chloro-phenylamino)-4-(5-hydroxy-1-pentylamino)-5-nitro-pyrimidine

[1095] HPLC/MS (Method B): RT=2,97 min.; [M+H]+=352,2

[1096] (160)2-(4-chloro-phenylamino)-4-(1,1-dimethyl-2-hydroxy-1-ethylamino)-5-nitro-pyrimidine

[1097] HPLC/MS (Method B): RT=2,66 min.; [M+H]+=338,17

[1098] (161)2-(4-carboxyphenylamino)-4-(2-(3-hydroxy-phenyl)-1-ethylamino)-5-nitro-pyrimidine

[1099] HPLC/MS (Method B): RT=2,4 min.; [M+H]+=396,3

[1100] (162)2-(benzylamino)-4-(4-aminomethyl-cyclohexylmethylamino)-5-nitro-pyrimidine

[1101] Melting point: 169° C.

[1102] (163)2-(benzylamino)-4-(4-aminomethyl-cyclohexylmethylamino)-5-trifluoromethyl-pyrimidine

[1103] Melting point: 119° C.

[1104] (164)2-(4-carboxyphenylamino)-4-(2-(4-hydroxy-phenyl)-1-ethylamino)-5-nitro-pyrimidine

[1105] HPLC/MS (Method B): RT=2,36 min.; [M+H]+=396,2

[1106] (165)2-(2-chlorobenzylamino)-4-(4-aminomethyl-cyclohexylmethylamino)-5-nitro-pyrimidine

[1107] Melting point: 189° C.

[1108] (166)2-(3-carboxyphenylamino)-4-(2-(4-hydroxy-phenyl)-1-ethylamino)-5-nitro-pyrimidine

[1109] HPLC/MS (Method B): RT=2,34 min.; [M+H]+=396,2

[1110] (167)2-(4-chloro-phenylamino)-4-(4-aminomethyl-cyclohexylmethylamino)-5-nitro-pyrimidine

[1111] (168)2-(3-carboxyphenylamino)-4-(2-(3-hydroxy-phenyl)-1-ethylamino)-5-nitro-pyrimidine

[1112] HPLC/MS (Method B): RT=2,41 min.; [M+H]+=396,3

[1113] (169)2-(4-chloro-phenylamino)-4-(2-(imidazolidin-2-on-1-yl)-1-ethylamino)-5-nitro-pyrimidine

[1114] HPLC/MS (Method B): RT=2,5 min.; [M+H]+=378,2

[1115] (170)2-(4-bromo-phenylamino)-4-(2-(1H-imidazol-4-yl)-1-ethylamino)-5-trifluoromethyl-pyrimidine

[1116] HPLC/MS (Method B): RT=2 min.; [M+H]+=427.1

[1117] (171)2-(3-bromo-phenylamino)-4-(4-aminomethyl-cyclohexylmethylamino)-5-nitro-pyrimidine

[1118] HPLC/MS (Method B): RT=2,56 min.; [M+H]+=435,2

[1119] (172)2-(4-bromo-phenylamino)-4-(4-aminomethyl-cyclohexylmethylamino)-5-nitro-pyrimidine

[1120] HPLC/MS (Method B): RT=2,66 min.; [M+H]+=435,2

[1121] (173)2-(4-chloro-phenylamino)-4-(1-methyl-4-piperidinyl-amino)-5-nitro-pyrimidine

[1122] HPLC/MS (Method B): RT=2,24 min.; [M+H]+=363,2

[1123] (174)2-(4-chloro-phenylamino)-4-(6-amino-1-hexylamino)-5-nitro-pyrimidine

[1124] HPLC/MS (Method B): RT=2,46 min.; [M+H]+=365,2

[1125] (175)2-(4-chloro-phenylamino)-4-(3-aminomethyl-cyclohexylmethylamino)-5-nitro-pyrimidine

[1126] HPLC/MS (Method B): RT=2,56 min.; [M+H]+=391,2

[1127] (176)2-(4-benzylaminocarbonyl-phenylamino)-4-(4-acetyl-1-piperazinyl)-5-nitro-pyrimidine

[1128] HPLC/MS (Method B): RT=2,53 min.; [M+H]+=476,2

[1129] (177)2-(3-carboxy-phenylamino)-4-(4-aminosulphonyl-benzylamino)-5-nitro-pyrimidine

[1130] HPLC/MS (Method B): RT=2,31 min.; [M+H]+=445.1

[1131] (178)2-(4-chloro-phenylamino)-4-[N-(1-methyl-4-piperidinyl-methyl)-N-methyl-amino]-5-nitro-pyrimidine

[1132] HPLC/MS (Method B): RT=2,31 min.; [M+H]+=391,2

[1133] (179)2-(3-carboxy-phenylamino)-4-(4-aminomethyl-cyclohexylmethylamino)-5-nitro-pyrimidine(mixture of isomers)

[1134] HPLC/MS (Method B): RT=1,97 min.; [M+H]+=401,2

[1135] (180)2-(3-ethoxycarbonyl-phenylamino)-4-(4-aminomethyl-cyclohexylmethylamino)-5-nitro-pyrimidine(mixture of isomers)

[1136] HPLC/MS (Method B): RT=2,42 min.; [M+H]+=429,3

[1137] (181)2-(4-benzylaminocarbonyl-phenylamino)-4-(4-carboxy-4-phenyl-1-piperidinyl)-5-nitro-pyrimidine

[1138] HPLC/MS (Method B): RT=3,11 min.; [M+H]+=553,3

[1139] (182)2-(3,4-dichlorophenylamino)-4-(2-(3-carboxy-2-methoxy-phenyl)-1-ethylamino)-5-trifluoromethyl-pyrimidine

[1140] HPLC/MS (Method B): RT=2,96 min.; [M+H]+=501,2

[1141] (183)2-(4-chlorophenylamino)-4-(7-methyl-2,7-diaza-spiro[4.4]non-2-yl)-5-nitro-pyrimidine

[1142] HPLC/MS (Method B): RT=2,34 min.; [M+H]+=389,2

[1143] (184)2-(4-carboxy-phenylamino)-4-(4-hydroxy-benzylamino)-5-nitro-pyrimidine

[1144] HPLC/MS (Method B): RT=2,2 min.; [M+H]+=382.1

[1145] (185)2-(3,4-dichlorophenylamino)-4-(3-carboxy-cyclohexylamino)-5-trifluoromethyl-pyrimidineHPLC/MS (Method B): RT=2,9 min.; [M+H]+=449,2

[1146] (186)2-(3,4-dichlorophenylamino)-4-(4-aminomethyl-cyclohexylmethylamino)-5-trifluoromethyl-pyrimidine

[1147] HPLC/MS (Method B): RT=2,35 min.; [M+H]+=448.1

[1148] (187)2-(3,4-dichlorophenylamino)-4-(1-carboxy-2,2-diphenyl-1-ethylamino)-5-trifluoromethyl-pyrimidine

[1149] HPLC/MS (Method B): RT=3,17 min.; [M+H]+=547,28

[1150] (188)2-(3,4-dichlorophenylamino)-4-(3-aminomethyl-cyclohexylmethylamino)-5-trifluoromethyl-pyrimidine

[1151] HPLC/MS (Method B): RT=2.15 min.; [M+H]+=448.0

[1152] Melting point: 140-142° C.

[1153] R_(f)=0,08 (silica gel; methylene chloride:methanol=4:1)

[1154] HPLC/MS (Method G): RT=3.78 min.; [M+H]+=449; Abs. λ max=260.8 nm

[1155] (189)2-(benzylamino)-4-(2-(3-hydroxyphenyl)-1-ethylamino)-5-trifluoromethyl-pyrimidine

[1156] (190)2-(4-chloro-phenylamino)-4-(3-hydroxy-piperidin-1-yl)-5-nitro-pyrimidine

[1157] HPLC/MS (Method B): RT=2,9 min.; [M+H]+=350,2

[1158] (191)2-(4-chloro-phenylamino)-4-(trans-4-hydroxy-cyclohexylamino)-5-nitro-pyrimidine

[1159] HPLC/MS (Method B): RT=2,92 min.; [M+H]+=364,2

[1160] (192)2-(4-chloro-phenylamino)-4-(4-amino-cyclohexylamino)-5-nitro-pyrimidine

[1161] HPLC/MS (Method B): RT=2,4 min.; [M+H]+=393,2

[1162] (193)2-(4-chloro-phenylamino)-4-(4-dimethylamino-cyclohexylamino)-5-nitro-pyrimidine

[1163] HPLC/MS (Method B): RT=2,36 min.; [M+H]+=391,2

[1164] (194)2-(4-chloro-phenylamino)-4-((1R)-1-carboxy-1-ethylamino)-5-nitro-pyrimidine

[1165] HPLC/MS (Method B): RT=2,51 min.; [M+H]+=338,14

[1166] (195)2-(4-chloro-phenylamino)-4-(3-amino-propylamino)-5-nitro-pyrimidine

[1167] HPLC/MS (Method B): RT=2,15 min.; [M+H]+=323.1

[1168] (196)2-(4-chloro-phenylamino)-4-(3-(3-aminopropoxy-1-propylamino)-5-nitro-pyrimidine

[1169] (197)2-(4-chlorine-phenylamino)-4-(4-aminomethyl-piperidin-1-yl)-5-nitro-pyrimidine

[1170] (198)2-(4-chloro-phenylamino)-4-(3-(isopropylamino)-1-propylamino)-5-nitro-pyrimidine

[1171] HPLC/MS (Method B): RT=2,32 min.; [M+H]+=365.1

[1172] (199)2-(4-chloro-phenylamino)-4-(2-(4-(2-hydroxyethyl)-piperazin-1-yl)-1-ethylamino))-5-nitro-pyrimidine

[1173] (200)2-(4-chloro-phenylamino)-4-(3-(3-hydroxy-8-methyl-8-aza-bicyclo[3.2.1]octyl)-methylamino)-5-nitro-pyrimidine

[1174] HPLC/MS (Method B): RT=2,17 min.; [M+H]+419,2

[1175] (201)2-(4-chloro-phenylamino)-4-(3-hydroxy-1,3-dihydro-2-oxo-indol-3-yl-methylamino)-5-nitro-pyrimidine

[1176] (202)2-(4-chloro-phenylamino)-4-(2-(3-carboxy-2-methoxy-phenyl)-1-ethylamino)-5-nitro-pyrimidine

[1177] HPLC/MS (Method B): RT=3,2 min.; [M+H]+=444.1

[1178] (203)2-(4-chloro-phenylamino)-4-(3-hydroxymethyl-piperidin-1-yl)-5-nitro-pyrimidine

[1179] HPLC/MS (Method B): RT=2,97 min.; [M+H]+=364,2

[1180] (204)2-(4-chloro-phenylamino)-4-(bis-(2-hydroxy-ethyl)-amino)-5-nitro-pyrimidine

[1181] HPLC/MS (Method B): RT=2,41 min.; [M+H]+=354.1

[1182] (205)2-(4-chloro-phenylamino)-4-(4-nitrobenzylamino)-5-nitro-pyrimidine

[1183] HPLC/MS (Method B): RT=3,49 min.; [M+H]+=401,2

[1184] (206)2-(4-chloro-phenylamino)-4-(2-aminocarbonyl-1-ethylamino)-5-nitro-pyrimidine

[1185] (207)2-(4-chloro-phenylamino)-4-(1-carboxy-2-(1H-imidazol-4-yl)-1-ethylamino)-5-nitro-pyrimidine

[1186] HPLC/MS (Method B): RT=1,67 min.; [M+H]+=404,15

[1187] (208)2-(4-chloro-phenylamino)-4-(1-carboxy-2,2-diphenyl-1-ethylamino)-5-nitro-pyrimidine

[1188] HPLC/MS (Method B): RT=3,25 min.; [M+H]+=490,2

[1189] (209)2-(4-chloro-phenylamino)-4-(3-carboxy-cyclohexylamino)-5-nitro-pyrimidine

[1190] HPLC/MS (Method B): RT=3,15 min.; [M+H]+=392,2

[1191] (210)2-(4-chloro-phenylamino)-4-(4-(2-carboxy-1-ethyl)-cyclohexylamino)-5-nitro-pyrimidine

[1192] HPLC/MS (Method B): RT=3,41 min.; [M+H]+=420,3

[1193] (211)2-(4-chloro-phenylamino)-4-(2-(3-hydroxyphenyl)-1-ethylamino)-5-nitro-pyrimidine

[1194] HPLC/MS (Method B): RT=3,29 min.; [M+H]+=386,2

[1195] (212)2-(4-chloro-phenylamino)-4-(2-(1H-pyrazol-4-yl)-1-ethylamino)-5-nitro-pyrimidine

[1196] HPLC/MS (Method B): RT=2,38 min.; [M+H]+=360.1

[1197] (213)2-(4-chloro-phenylamino)-4-(3-(2-aza-bicyclo[2.2.1]hept-5-en-2-yl)-propylamino)-5-nitro-pyrimidine

[1198] (214)2-(4-chloro-phenylamino)-4-(1-methyl-piperidin-4-yl-methylamino)-5-nitro-pyrimidine

[1199] HPLC/MS (Method B): RT=2,28 min.; [M+H]+=377,2

[1200] (215)2-(4-chloro-phenylamino)-4-(cis-4-hydroxy-cyclohexylamino)-5-nitro-pyrimidine

[1201] HPLC/MS (Method B): RT=2,92 min.; [M+H]+=364,2

[1202] (216)2-(4-chloro-phenylamino)-4-(4-dimethylaminomethyl-cyclohexylmethylamino)-5-nitro-pyrimidine

[1203] HPLC/MS (Method B): RT=2,15 min.; [M+H]+=357.1

[1204] (217)2-(4-chloro-phenylamino)-4-(2-(imidazol-1-yl)-1-ethylamino)-5-nitro-pyrimidine

[1205] HPLC/MS (Method B): RT=2,26 min.; [M+H]+=371.1

[1206] (218)2-(3,4-dichloro-phenylamino)-4-(6-amino-1-hexylamino)-5-trifluoromethyl-pyrimidine

[1207] HPLC/MS (Method B): RT=2,31 min.; [M+H]+422.1

[1208] (219)2-(3,4-dichloro-phenylamino)-4-(N-(1-methyl-piperidin-4-yl)-N-methyl-amino)-5-trifluoromethyl-pyrimidine

[1209] HPLC/MS (Method B): RT=2,46 min.; [M+H]+=434.1

[1210] (220)2-(3,4-dichloro-phenylamino)-4-(N-methyl-N-(2-hydroxybenzyl)-amino)-5-trifluoromethyl-pyrimidine

[1211] HPLC/MS (Method B): RT=3,3 min.; [M+H]+=443.1

[1212] (221)2-(3,4-dichlorophenylamino)-4-(N-methyl-N-(2-cyano-1-ethyl)-amino)-5-trifluoromethyl-pyrimidine

[1213] HPLC/MS (Method B): RT=3,27 min.; [M+H]+=390.1

[1214] (222)2-(3,4-dichlorophenylamino)-4-(3-(4-(1-pyrrolidinyl)-butyl)-piperidin-1-yl)-5-trifluoromethyl-pyrimidine

[1215] HPLC/MS (Method B): RT=2,87 min.; [M+H]+=516.1

[1216] (223)2-(3,4-dichlorophenylamino)-4-((2S)-2-hydroxymethyl-pyrrolidin-1-yl)-5-trifluoromethyl-pyrimidine

[1217] HPLC/MS (Method B): RT=2,85 min.; [M+H]+=407,2

[1218] (224)2-(3,4-dichlorophenylamino)-4-((2R)-2-hydroxymethyl-pyrrolidin-1-yl)-5-trifluoromethyl-pyrimidine

[1219] HPLC/MS (Method B): RT=2,62 min.; [M+H]+=407,2

[1220] (225)2-(3,4-dichlorophenylamino)-4-(2-(imidazolidin-2-on-1-yl)-1-ethylamino)-5-trifluoromethyl-pyrimidine

[1221] HPLC/MS (Method B): RT=2,49 min.; [M+H]+=435.1

[1222] (226)2-(3,4-dichlorophenylamino)-4-(4-(N-acetyl-N-methyl-aminomethyl)-piperidin-1-yl)-5-trifluoromethyl-pyrimidine

[1223] HPLC/MS (Method B): RT=2,59 min.; [M+H]+=476,3

[1224] (227)2-(3,4-dichlorophenylamino)-4-[N-(1-methyl-4-piperidinyl-methyl)-N-methyl-amino]-5-trifluoromethyl-pyrimidine

[1225] HPLC/MS (Method B): RT=2,4 min.; [M+H]+=434,2

[1226] (228)2-(3,4-dichlorophenylamino)-4-(4-methylpiperazino)-5-trifluoromethyl-pyrimidine

[1227] HPLC/MS (Method B): RT=2,41 min.; [M+H]+=406,2

[1228] (229)2-(3,4-dichlorophenylamino)-4-(4-hydroxy-1-piperidinyl)-5-trifluoromethyl-pyrimidine

[1229] HPLC/MS (Method B): RT=2,63 min.; [M+H]+=407,2

[1230] (230)2-(3,4-dichlorophenylamino)-4-(2-dimethylamino-1-ethylamino)-5-trifluoromethyl-pyrimidine

[1231] HPLC/MS (Method B): RT=2,24 min.; [M+H]+=394.1

[1232] (231)2-(3,4-dichlorophenylamino)-4-(3-(4-morpholinyl)-1-propylamino)-5-trifluoromethyl-pyrimidine

[1233] HPLC/MS (Method B): RT=2,15 min.; [M+H]+=450.1

[1234] (232)2-(3,4-dichlorophenylamino)-4-(2-carboxy-1-ethylamino)-5-trifluoromethyl-pyrimidine

[1235] HPLC/MS (Method B): RT=2,34 min.; [M+H]+=395,2

[1236] (233)2-(3,4-dichlorophenylamino)-4-(3-(1H-1-imidazolyl)-1-propylamino)-5-trifluoromethyl-pyrimidine

[1237] HPLC/MS (Method B): RT=2,01 min.; [M+H]+=431.1

[1238] (234)2-(3,4-dichlorophenylamino)-4-(3-dimethylamino-1-propylamino)-5-trifluoromethyl-pyrimidine

[1239] HPLC/MS (Method B): RT=1,87 min.; [M+H]+=408.1

[1240] (235)2-(3,4-dichlorophenylamino)-4-(2-diisopropylamino-1-ethylamino)-5-trifluoromethyl-pyrimidine

[1241] HPLC/MS (Method B): RT=2,5 min.; [M+H]+=450,3

[1242] (236)2-(3,4-dichlorophenylamino)-4-(bis-(2-methoxyethyl)amino)-5-trifluoromethyl-pyrimidine

[1243] HPLC/MS (Method B): RT=3,44 min.; [M+H]+=439,2

[1244] (237)2-(3,4-dichlorophenylamino)-4-(N-methyl-N-(2-methylamino-1-ethyl)-amino)-5-trifluoromethyl-pyrimidine

[1245] HPLC/MS (Method B): RT=2,56 min.; [M+H]+=394,0

[1246] (238)2-(3,4-dichlorophenylamino)-4-(2-(4-pyridyl)-1-ethylamino)-5-trifluoromethyl-pyrimidine

[1247] HPLC/MS (Method B): RT=2,17 min.; [M+H]+=428.1

[1248] (239)2-(3,4-dichlorophenylamino)-4-(4-aminosulphonyl-benzylamino)-5-trifluoromethyl-pyrimidine

[1249] HPLC/MS (Method B): RT=2,72 min.; [M+H]+=492,2

[1250] (240)2-(3,4-dichlorophenylamino)-4-(2-acetylamino-ethylamino)-5-chloro-pyrimidine

[1251] Prepared analogously to Example 1(80).Melting point: 147° C.

[1252] Rf=0,12 (silica gel; methylene chloride:methanol=4:1)

[1253] HPLC/MS (Method G): RT=3,76 min.; [M+H]+=381; Abs. λ max=270,3 nm

[1254] (241)2-(3,4-dichlorophenylamino)-4-(4-pyridyl-methylamino)-5-trifluoromethyl-pyrimidine

[1255] HPLC/MS (Method B): RT=2,31 min.; [M+H]+=414,2

[1256] (242)2-(3,4-dichlorophenylamino)-4-((3-chloro-5-trifluoromethyl-2-pyridyl)-methylamino)-5-trifluoromethyl-pyrimidine

[1257] (243)2-(3,4-dichlorophenylamino)-4-((4-ethoxycarbonyl-1H-pyrazol-5-yl)-methylamino)-5-trifluoromethyl-pyrimidine

[1258] (244)2-(3,4-dichlorophenylamino)-4-(3-nitrobenzylamino)-5-trifluoromethyl-pyrimidine

[1259] HPLC/MS (Method B): RT=3,3 min.; [M+H]+=458,2

[1260] (245)2-(3,4-dichlorophenylamino)-4-(4-(2-carboxy-1-ethyl)-1-piperidinyl)-5-trifluoromethyl-pyrimidine

[1261] HPLC/MS (Method B): RT=3,11 min.; [M+H]+=463,2

[1262] (246)2-(3,4-dichlorophenylamino)-4-(3-(1-pyrrolidinyl)-1-propylamino)-5-trifluoromethyl-pyrimidine

[1263] HPLC/MS (Method B): RT=2,26 min.; [M+H]+=434.1

[1264] (247)2-(3,4-dichlorophenylamino)-4-(5-acetylamino-5-methoxycarbonyl-1-pentylamino)-5-trifluoromethyl-pyrimidine

[1265] HPLC/MS (Method B): RT=2,4 min.; [M+H]+=508,2

[1266] (248)2-(3,4-dichlorophenylamino)-4-((1-hydroxy-1-cyclohexyl)-methylamino)-5-trifluoromethyl-pyrimidine

[1267] HPLC/MS (Method B): RT=3,16 min.; [M+H]+=435.1

[1268] (249)2-(3,4-dichlorophenylamino)-4-(2-(1H-indol-3-yl)-1-ethylamino)-5-trifluoromethyl-pyrimidine

[1269] HPLC/MS (Method B): RT=3,26 min.; [M+H]+=466,2

[1270] (250)2-(3,4-dichlorophenylamino)-4-(2-(4-nitro-2-pyridyl-amino)-1-ethylamino)-5-trifluoromethyl-pyrimidine

[1271] HPLC/MS (Method B): RT=2,99 min.; [M+H]+=488.1

[1272] (251)2-(3,4-dichlorophenylamino)-4-(2-hydroxy-2-phenyl-1-ethylamino)-5-trifluoromethyl-pyrimidine

[1273] HPLC/MS (Method B): RT=3,02 min.; [M+H]+=443.1

[1274] (252)2-(3,4-dichlorophenylamino)-4-(2-phenylamino-1-ethylamino)-5-trifluoromethyl-pyrimidine

[1275] HPLC/MS (Method B): RT=3,16 min.; [M+H]+=442,2

[1276] (253)2-(3,4-dichlorophenylamino)-4-(2-(4-hydroxyphenyl)-1-ethylamino)-5-trifluoromethyl-pyrimidine

[1277] HPLC/MS (Method B): RT=2,91 min.; [M+H]+=443,2

[1278] (254)2-(3,4-dichlorophenylamino)-4-(2-(4-aminosulphonylphenyl)-1-ethylamino)-5-trifluoromethyl-pyrimidine

[1279] HPLC/MS (Method B): RT=2,74 min.; [M+H]+=506.1

[1280] (255)2-(3,4-dichlorophenylamino)-4-(2-(1-naphthylamino)-1-ethylamino)-5-trifluoromethyl-pyrimidine

[1281] HPLC/MS (Method B): RT=3,6 min.; [M+H]+=492,2

[1282] (256)2-(3,4-dichlorophenylamino)-4-(2-(4-nitrophenyl)-1-ethylamino)-5-trifluoromethyl-pyrimidine

[1283] HPLC/MS (Method B): RT=3,33 min.; [M+H]+=472,2

[1284] (257)2-(3,4-dichlorophenylamino)-4-(3-ethoxycarbonyl-1-propylamino)-5-trifluoromethyl-pyrimidine

[1285] HPLC/MS (Method B): RT=3,14 min.; [M+H]+=437,2

[1286] (258)2-(3,4-dichlorophenylamino)-4-(aminocarbonylmethylamino)-5-trifluoromethyl-pyrimidine

[1287] HPLC/MS (Method B): RT=2,33 min.; [M+H]+=380.1

[1288] (259)2-(3,4-dichlorophenylamino)-4-(2-acetylamino-ethylamino)-5-ethyl-pyrimidine

[1289] Melting point: 211-213° C.

[1290] R_(f)=0,04 (silica gel; methylene chloride:methanol=4:1)

[1291] HPLC/MS (Method F): RT=2,79 min.; [M+H]+=341; Abs. λ max=277,9 nm

[1292] (260)2-(3,4-dichlorophenylamino)-4-(2-tert.-butyloxycarbonylamino-1-ethylamino)-5-trifluoromethyl-pyrimidine

[1293] HPLC/MS (Method B): RT=2,96 min.; [M+H]+=466.1

[1294] (261)2-(3,4-dichlorophenylamino)-4-(1-ethyl-2-pyrrolidinyl-methylamino)-5-trifluoromethyl-pyrimidine

[1295] HPLC/MS (Method B): RT=2,52 min.; [M+H]+=434,2

[1296] (262)2-(3,4-dichlorophenylamino)-4-(2-(1-pyrrolidinyl)-1-ethylamino)-5-trifluoromethyl-pyrimidine

[1297] HPLC/MS (Method B): RT=2,33 min.; [M+H]+=420,2

[1298] (263)2-(3,4-dichlorophenylamino)-4-(2-tetrahydrofuryl-methylamino)-5-trifluoromethyl-pyrimidine

[1299] (264)2-(3,4-dichlorophenylamino)-4-(2-(1-piperidinyl)-1-ethylamino)-5-trifluoromethyl-pyrimidine

[1300] HPLC/MS (Method B): RT=2,4 min.; [M+H]+=434,2

[1301] (265)2-(3,4-dichlorophenylamino)-4-(2-hydroxy-1-propylamino)-5-trifluoromethyl-pyrimidine

[1302] HPLC/MS (Method B): RT=2,63 min.; [M+H]+=381.1

[1303] (266)2-(3,4-dichlorophenylamino)-4-(2,3-dihydroxy-1-propylamino)-5-trifluoromethyl-pyrimidine

[1304] HPLC/MS (Method B): RT=2,31 min.; [M+H]+=397,2

[1305] (267)2-(3,4-dichlorophenylamino)-4-(2-diethylamino-1-ethylamino)-5-trifluoromethyl-pyrimidine

[1306] HPLC/MS (Method B): RT=2,39 min.; [M+H]+=422.1

[1307] (268)2-(3,4-dichlorophenylamino)-4-(2-(2-hydroxyethoxy)-1-ethylamino)-5-trifluoromethyl-pyrimidine

[1308] HPLC/MS (Method B): RT=2,5 min.; [M+H]+=411,2

[1309] (269)2-(3,4-dichlorophenylamino)-4-(2-hydroxy-1-ethylamino)-5-trifluoromethyl-pyrimidine

[1310] HPLC/MS (Method B): RT=2,46 min.; [M+H]+=367,2

[1311] (270)2-(3,4-dichlorophenylamino)-4-(3-diethylamino-1-propylamino)-5-trifluoromethyl-pyrimidine

[1312] HPLC/MS (Method B): RT=2,26 min.; [M+H]+=436,2

[1313] (271)2-(3,4-dichlorophenylamino)-4-(3-hydroxy-1-propylamino)-5-trifluoromethyl-pyrimidine

[1314] HPLC/MS (Method B): RT=2,49 min.; [M+H]+=381,2

[1315] (272)2-(3,4-dichlorophenylamino)-4-(2-(1-methyl-1H-pyrrol-2-yl)-1-ethylamino)-5-trifluoromethyl-pyrimidine

[1316] HPLC/MS (Method B): RT=3,23 min.; [M+H]+=430.1

[1317] (273)2-(3,4-dichlorophenylamino)-4-(4-hydroxy-3-methoxy-benzylamino)-5-trifluoromethyl-pyrimidine

[1318] HPLC/MS (Method B): RT=2,89 min.; [M+H]+=459.1

[1319] (274)2-(3,4-dichlorophenylamino)-4-(2-methylsulphanyl-1-ethylamino)-5-trifluoromethyl-pyrimidine

[1320] HPLC/MS (Method B): RT=3,17 min.; [M+H]+=397.1

[1321] (275)2-(3,4-dichlorophenylamino)-4-(3-methoxy-1-propylamino)-5-trifluoromethyl-pyrimidine

[1322] HPLC/MS (Method B): RT=3,06 min.; [M+H]+=395,2

[1323] (276)2-(3,4-dichlorophenylamino)-4-(2,2-dimethyl-3-dimethylamino-1-propylamino)-5-trifluoromethyl-pyrimidine

[1324] HPLC/MS (Method B): RT=2,41 min.; [M+H]+=436.1

[1325] (277)2-(3,4-dichlorophenylamino)-4-(2,2-dimethyl-3-hydroxy-1-propylamino)-5-trifluoromethyl-pyrimidine

[1326] HPLC/MS (Method B): RT=3,03 min.; [M+H]+=409,2

[1327] (278)2-(3,4-dichlorophenylamino)-4-cyanomethylamino-5-trifluoromethyl-pyrimdine

[1328] HPLC/MS (Method B): RT=2,66 min.; [M+H]+=362,2

[1329] (279)2-(3,4-dichlorophenylamino)-4-(3-aminocarbonyl-1-piperidinyl)-5-trifluoromethyl-pyrimidine

[1330] HPLC/MS (Method B): RT=2,6 min.; [M+H]+=434,2

[1331] (280)2-(3,4-dichlorophenylamino)-4-(4-acetyl-1-piperazinyl)-5-trifluoromethyl-pyrimidine

[1332] HPLC/MS (Method B): RT=2,81 min.; [M+H]+=434,2

[1333] (281)2-(3,4-dichlorophenylamino)-4-(4-(1-piperidinyl)-1-piperidinyl)-5-trifluoromethyl-pyrimidine

[1334] HPLC/MS (Method B): RT=2,45 min.; [M+H]+=474,2

[1335] (282)2-(3,4-dichlorophenylamino)-4-(4-(morpholinocarbonylmethyl)-1-piperazinyl)-5-trifluoromethyl-pyrimidine

[1336] HPLC/MS (Method B): RT=2,41 min.; [M+H]+=519,2

[1337] (283)2-(3,4-dichlorophenylamino)-4-piperazino-5-trifluoromethyl-pyrimidine

[1338] HPLC/MS (Method B): RT=2,31 min.; [M+H]+=392,2

[1339] (284)2-(3,4-dichlorophenylamino)-4-(3-(4-(3-amino-1-propyl)-1-piperazinyl)-1-propylamino)-5-trifluoromethyl-pyrimidine

[1340] HPLC/MS (Method B): RT=1,7 min.; [M+H]+=506,2

[1341] (285)2-(3,4-dichloro-phenylamino)-4-(cis-4-carboxy-cyclohexylamino)-5-trifluoromethyl-pyrimidine

[1342] (286)2-(3,4-dichlorophenylamino)-4-(3-dibenzylamino-1-propylamino)-5-trifluoromethyl-pyrimidine

[1343] HPLC/MS (Method B): RT=2,65 min.; [M+H]+=560.1

[1344] (287)2-(3,4-dichloro-phenylamino)-4-(N-[4-methoxycarbonyl-cyclohexyl]-N-[3-pyridylmethyl]amino)-5-trifluoromethyl-pyrimidine

[1345] HPLC/MS (Method B): RT=2,5 min.; [M+H]+=554.1

[1346] (288)2-(3,4-dichlorophenylamino)-4-(2-acetylamino-ethylamino)-5-methoxymethyl-pyrimidine

[1347] (289)2-(3,4-dichlorophenylamino)-4-(2-phenyl-1-(4-phenyl-1-butyl-aminocarbonyl)-1-ethylamino)-5-trifluoromethyl-pyrimidine

[1348] HPLC/MS (Method B): RT=3,73 min.; [M+H]+=602,28

[1349] (290)2-(3,4-dichlorophenylamino)-4-(1-aminocarbonyl-2-(4-methoxyphenyl)1-ethylamino)-5-trifluoromethyl-pyrimidine

[1350] HPLC/MS (Method B): RT=2,61 min.; [M+H]+=500,24

[1351] (291)2-(3,4-dichlorophenylamino)-4-(1-dimethylaminomethylcarbonyl-4-piperidinyl-methylamino)-5-trifluoromethyl-pyrimidine

[1352] (292)2-(3,4-dichloro-phenylamino)-4-(N-ethyl-N-(4-pyridylmethyl)-amino)-5-trifluoromethyl-pyrimidine

[1353] HPLC/MS (Method B): RT=2,66 min.; [M+H]+=435,2

[1354] (293)2-(3,4-dichloro-phenylamino)-4-(3-phenyl-azepan-4-on-1-yl)-5-trifluoromethyl-pyrimidine

[1355] HPLC/MS (Method B): RT=2,49 min.; [M+H]+=381,2

[1356] (294)2-(3,4-dichlorophenylamino)-4-(2-(3-hydroxy-1-propyl)-1-piperidinyl)-5-trifluoromethyl-pyrimidine

[1357] HPLC/MS (Method B): RT=3,2 min.; [M+H]+=449,0

[1358] (295)2-(3,4-dichlorophenylamino)-4-(4-(8-methoxy-3,4-dihydro-1H-quinazolin-2-on-3-yl)-1-piperidinyl)-5-trifluoromethyl-pyrimidine

[1359] HPLC/MS (Method B): RT=3.1 min.; [M+H]+=567,08

[1360] (296)2-(3,4-dichlorophenylamino)-4-(4-(2-nitrophenyl)-1-piperazinyl)-5-trifluoromethyl-pyrimidine

[1361] Melting point: 228-229° C.

[1362] Rf=0,07 (silica gel; methylene chloride:methanol=4:1)

[1363] HPLC/MS (Method G): RT=2,61 min.; [M+H]+=409; Abs. λ max=276 nm

[1364] (297)2-(3,4-dichlorophenylamino)-4-(4-(3,4-dimethoxyphenyl)-1-piperazinyl)-5-trifluoromethyl-pyrimidine

[1365] HPLC/MS (Method B): RT=3,02 min.; [M+H]+=443.1

[1366] (298)2-(3,4-dichlorophenylamino)-4-(4-(4-cyanophenyl)-1-piperazinyl)-5-trifluoromethyl-pyrimidine

[1367] HPLC/MS (Method B): RT=2,41 min.; [M+H]+=396,3

[1368] (299)2-(3,4-dichlorophenylamino)-4-(1-benzyl-3-pyrrolidinyl-amino)-5-trifluoromethyl-pyrimidine

[1369] HPLC/MS (Method B): RT=2,54 min.; [M+H]+=482,2

[1370] (300)2-(3,4-dichlorophenylamino)-4-(1-hydroxy-2-propylamino)-5-trifluoromethyl-pyrimidine

[1371] HPLC/MS (Method B): RT=2,48 min.; [M+H]+=381,2

[1372] (301)2-(3,4-dichlorophenylamino)-4-(3-(1-piperidinyl)-1-propylamino)-5-trifluoromethyl-pyrimidine

[1373] HPLC/MS (Method B): RT=2,08 min.; [M+H]+=448.1

[1374] (302)2-(3,4-dichlorophenylamino)-4-(1-benzyl-4-piperidinyl-amino)-5-trifluoromethyl-pyrimidine

[1375] HPLC/MS (Method B): RT=2,41 min.; [M+H]+=496,2

[1376] (303)2-(3,4-dichlorophenylamino)-4-(4-aminomethyl-benzylamino)-5-trifluoromethyl-pyrimidine

[1377] HPLC/MS (Method B): RT=2,14 min.; [M+H]+=442.1

[1378] (304)2-(3,4-dichlorophenylamino)-4-(4-aminobutylamino)-5-trifluoromethyl-pyrimidine

[1379] HPLC/MS (Method B): RT=2,11 min.; [M+H]+=394.1

[1380] (305)2-(3,4-dichlorophenylamino)-4-(3-amino-2,2-dimethyl-1-propylamino)-5-trifluoromethyl-pyrimidine

[1381] HPLC/MS (Method B): RT=2,4 min.; [M+H]+=408.1

[1382] (306)2-(3,4-dichlorophenylamino)-4-(trans-2-amino-cyclohexylamino)-5-trifluoromethyl-pyrimidine

[1383] HPLC/MS (Method B): RT=2,61 min.; [M+H]+=420.1

[1384] (307)2-(3,4-dichlorophenylamino)-4-(2-(2-(2-amino-1-ethoxy)-1-ethoxy)-1-ethylamino)-5-trifluoromethyl-pyrimidine

[1385] HPLC/MS (Method B): RT=2,25 min.; [M+H]+=454,0

[1386] (308)2-(3,4-dichlorophenylamino)-4-(3-amino-benzylamino)-5-trifluoromethyl-pyrimidine

[1387] HPLC/MS (Method B): RT=2,16 min.; [M+H]+=428,2

[1388] (309)2-(3,4-dichlorophenylamino)-4-(3-amino-2-hydroxy-1-propylamino)-5-trifluoromethyl-pyrimidine

[1389] HPLC/MS (Method B): RT=2,11 min.; [M+H]+=396.1

[1390] (310)2-(3,4-dichlorophenylamino)-4-(2-(2-amino-1-ethylsulphanyl)-1-ethylamino)-5-trifluoromethyl-pyrimidine

[1391] HPLC/MS (Method B): RT=2,28 min.; [M+H]+=426,0

[1392] (311)2-(3,4-dichlorophenylamino)-4-(N-[2-dimethylamino-1-ethyl]-N-ethyl-amino)-5-trifluoromethyl-pyrimidine

[1393] HPLC/MS (Method B): RT=2,76 min.; [M+H]+=422.1

[1394] (312)2-(3,4-dichlorophenylamino)-4-(N-[3-dimethylamino-1-propyl]-N-methyl-amino)-5-trifluoromethyl-pyrimidine

[1395] HPLC/MS (Method B): RT=2,39 min.; [M+H]+=422,0

[1396] (313)2-(3,4-dichlorophenylamino)-4-(3-(4-methyl-1-piperazinyl)-1-propylamino)-5-trifluoromethyl-pyrimidine

[1397] HPLC/MS (Method B): RT=2,09 min.; [M+H]+=463.1

[1398] (314)2-(3,4-dichloro-phenylamino)-4-(N-[2-cyano-1-ethyl]-N-[3-pyridylmethyl]-amino)-5-trifluoromethyl-pyrimidine

[1399] HPLC/MS (Method B): RT=2,4 min.; [M+H]+=467,0

[1400] (315)2-(3,4-dichloro-phenylamino)-4-(4-(2-pyridyl)-1-piperazinyl)-5-trifluoromethyl-pyrimidine

[1401] HPLC/MS (Method B): RT=2,48 min.; [M+H]+=469.1

[1402] (316)2-(3,4-dichloro-phenylamino)-4-(4-[bis-(4-methoxy-phenyl)]-methyl-1-piperazinyl)-5-trifluoromethyl-pyrimidine

[1403] (317)2-(3,4-dichloro-phenylamino)-4-(4-(3-methoxy-phenyl)-1-piperazinyl)-5-trifluoromethyl-pyrimidine

[1404] HPLC/MS (Method B): RT=2,4 min.; [M+H]+=396,3

[1405] (318)2-(3,4-dichloro-phenylamino)-4-(N-benzyl-N-[2-cyano-1-ethyl]-amino)-5-trifluoromethyl-pyrimidine

[1406] HPLC/MS (Method B): RT=3,92 min.; [M+H]+=466,2

[1407] (319)2-(3,4-dichloro-phenylamino)-4-(N-benzyl-N-[2-hydroxy-1-ethyl]-amino)-5-trifluoromethyl-pyrimidine

[1408] HPLC/MS (Method B): RT=3,4 min.; [M+H]+=457.1

[1409] (320)2-(3,4-dichlorophenylamino)-4-(3-carboxy-1-propyl-amino)-5-trifluoromethyl-pyrimidine

[1410] (321)2-(3,4-dichloro-phenylamino)-4-(N-benzyl-N-[ethoxycarbonylmethyl]-amino)-5-trifluoromethyl-pyrimidine

[1411] HPLC/MS (Method B): RT=4,11 min.; [M+H]+=499,2

[1412] (322)2-(3,4-dichloro-phenylamino)-4-(N-[4-nitrobenzyl]-N-propyl-amino)-5-trifluoromethyl-pyrimidine

[1413] HPLC/MS (Method B): RT=4,03 min.; [M+H]+=500,2

[1414] (323)2-(3,4-dichloro-phenylamino)-4-(cyano-phenyl-methylamino)-5-trifluoromethyl-pyrimidine

[1415] (324)2-(3,4-dichloro-phenylamino)-4-(N-benzyl-N-[4-hydroxy-1-butyl]-amino)-5-trifluoromethyl-pyrimidine

[1416] HPLC/MS (Method B): RT=3,43 min.; [M+H]+=485,2

[1417] (325)2-(3,4-dichloro-phenylamino)-4-(N-benzyl-N-[2-hydroxymethyl-1-cyclohexyl]-amino)-5-trifluoromethyl-pyrimidine

[1418] HPLC/MS (Method B): RT=2,8 min.; [M+H]+=525,26

[1419] (326) tert-butylN-1-[2-(3,4-dichloro-phenylamino)-5-trifluoromethyl-pyrimidin-4-yl]-pyrrolidin-3-yl)-carbaminate

[1420] Prepared analogously to Example 1(80)

[1421] Melting point: 198-200° C.

[1422] Rf=0,44 (silica gel; methylene chloride:methanol=99:1)

[1423] HPLC/MS (Method K): RT=4,37 min.; [M+H]+=493; Abs. λ max=270,3 nm

[1424] (327)2-(3,4-dichloro-phenylamino)-4-((1S)-1-carboxy-2-hydroxy-1-ethyl-amino)-5-trifluoromethyl-pyrimidine

[1425] HPLC/MS (Method B): RT=2 min.; [M+H]+=411

[1426] (328)2-(3,4-dichloro-phenylamino)-4-(5-carboxy-1-pentylamino)-5-trifluoromethyl-pyrimidine

[1427] HPLC/MS (Method B): RT=2,7 min.; [M+H]+=437,0

[1428] (329)2-(3,4-dichloro-phenylamino)-4-(2-aminocarbonyl-1-carboxy-1-ethylamino)-5-trifluoromethyl-pyrimidine

[1429] (330)2-(3,4-dichloro-phenylamino)-4-(2-carboxy-2-propylamino)-5-trifluoromethyl-pyrimidine

[1430] HPLC/MS (Method B): RT=2,5 min.; [M+H]+=409

[1431] (331)2-(3,4-dichloro-phenylamino)-4-(1-carboxy-3-methyl-1-propylamino)-5-trifluoromethyl-pyrimidine

[1432] (332)2-(3,4-dichloro-phenylamino)-4-((1R)-1-carboxy-2-hydroxy-1-ethylamino)-5-trifluoromethyl-pyrimidine

[1433] (333)2-(3,4-dichlorophenylamino)-4-(4-(2-amino-1-ethyl)-1-piperazinyl)-5-trifluoromethyl-pyrimidine

[1434] HPLC/MS (Method B): RT=2,36 min.; [M+H]+=435,2

[1435] (334)2-(3,4-dichlorophenylamino)-4-(3,5-dimethyl-1-piperazinyl)-5-trifluoromethyl-pyrimidine

[1436] HPLC/MS (Method B): RT=2,7 min.; [M+H]+=420.1

[1437] (335)2-(3,4-dichlorophenylamino)-4-(cis-2-amino-cyclohexylamino)-5-trifluoromethyl-pyrimidine

[1438] HPLC/MS (Method B): RT=2,68 min.; [M+H]+=420,2

[1439] (336)2-(3,4-dichloro-phenylamino)-4-(N-methyl-N-[3-methylamino-1-propyl]-amino)-5-trifluoromethyl-pyrimidine

[1440] (337)2-(3,4-dichloro-phenylamino)-4-(3-hydroxy-8-aza-bicyclo[3.2.1]oct-8-yl)-5-trifluoromethyl-pyrimidine

[1441] HPLC/MS (Method B): RT=2,75 min.; [M+H]+=433,2

[1442] (338)2-(3,4-dichloro-phenylamino)-4-(3-amino-1-pyrrolidinyl)-5-trifluoromethyl-pyrimidine

[1443] HPLC/MS (method B): RT=2.24 min.; [M+H]+=392,2 melting point:157-158° C.

[1444] R_(f)=0, 03 (silica gel; methylene chloride:methanol=9:1)

[1445] HPLC/MS (method G): RT=3.63 min.; [M+H]+=393; Abs. λ max=272,2 nm

[1446] (339)2-(3,4-dichlorophenylamino)-4-(4-benzyloxycarbonyl-1-piperazinyl)-5-trifluoromethyl-pyrimidine

[1447] HPLC/MS (method B): RT=3.99 min.; [M+H]+=526,2

[1448] (340)2-(3,4-dichlorophenylamino)-4-(3-(2-(3-amino-1-propoxy)-1-ethoxy)-1-propylamino)-5-trifluoromethyl-pyrimidine

[1449] HPLC/MS (method B): RT=2.35 min.; [M+H]+=482,1

[1450] (341)2-(3,4-dichlorophenylamino)-4-(N-benzyl-N-[2-hydroxy-1-phenyl-1-ethyl]-amino)-5-trifluoromethyl-pyrimidine

[1451] HPLC/MS (method B): RT=3.27 min.; [M+H]+=533,0

[1452] (342)2-(3,4-dichlorophenylamino)-4-(1-homopiperazinyl)-5-trifluoromethyl-pyrimidine

[1453] HPLC/MS (method B): RT=2.48 min.; [M+H]+=406,1

[1454] (343)2-(3,4-dichlorophenylamino)-4-(2-(2-(2-hydroxy-1-ethoxy)-1-ethoxy)-1-ethylamino)-5-trifluoromethyl-pyrimidine

[1455] HPLC/MS (method B): RT=2.56 min.; [M+H]+=455,2

[1456] (344)2-(3,4-dichlorophenylamino)-4-(2-(3-methoxycarbonylphenyl)-1-ethyl-amino)-5-trifluoromethyl-pyrimidine

[1457] HPLC/MS (method B): RT=3.37 min.; [M+H]+=485,2

[1458] (345)2-(3,4-dichloro-phenylamino)-4-(2-hydroxy-3-(4-morpholinyl)-1-propyl-amino)-5-trifluoromethyl-pyrimidine

[1459] HPLC/MS (method B): RT=2.19 min.; [M+H]+=466,1

[1460] (346)2-(3,4-dichlorophenylamino)-4-(N-methyl-N-[2-nitrobenzyl]-amino)-5-trifluoromethyl-pyrimidine

[1461] HPLC/MS (method B): RT=3.7 min.; [M+H]+=472,1

[1462] (347)2-(3,4-dichlorophenylamino)-4-(2-carboxy-1-phenyl-1-ethyl-amino)-5-trifluoromethyl-pyrimidine

[1463] HPLC/MS (method B): RT=3.15 min.; [M+H]+=471,1

[1464] (348)2-(3,4-dichlorophenylamino)-4-(N-methyl-N-[6-[N-methyl-N-(2-phenyl-1-ethyl)-amino]-1-hexyl]-amino)-5-trifluoromethyl-pyrimidine

[1465] HPLC/MS (method B): RT=2.92 min.; [M+H]+=554,1

[1466] (349)2-(3,4-dichlorophenylamino)-4-(2-(2-(2-amino-1-ethyl)-phenyl)-1-ethyl-amino)-5-trifluoromethyl-pyrimidine

[1467] HPLC/MS (method B): RT=2.27 min.; [M+H]+=470,0

[1468] (350)2-(3,4-dichlorophenylamino)-4-(N-[2-diethylamino-1-ethyl]-N-ethyl-amino)-5-trifluoromethyl-pyrimidine

[1469] HPLC/MS (method B): RT=2.86 min.; [M+H]+=450,1

[1470] (351)2-(3,4-dichlorophenylamino)-4-(2-ethoxycarbonyl-1-piperidinyl)-5-trifluoromethyl-pyrimidine

[1471] HPLC/MS (method B): RT=4.01 min.; [M+H]+=463,2

[1472] (352)2-(3,4-dichlorophenylamino)-4-(4-methyl-1-homopiperazinyl)-5-trifluoromethyl-pyrimidine

[1473] HPLC/MS (method B): RT=2.52 min.; [M+H]+=420,1

[1474] (353)2-(3,4-dichlorophenylamino)-4-(N-cyanomethyl-N-butyl-amino)-5-trifluoromethyl-pyrimidine

[1475] (354)2-(3,4-dichlorophenylamino)-4-(N-[2-dimethylamino-1-ethyl]-N-methyl-amino)-5-trifluoromethyl-pyrimidine

[1476] HPLC/MS (method B): RT=2.58 min.; [M+H]+=408,1

[1477] (355)2-(3,4-dichlorophenylamino)-4-(2-(1-pyrrolidinyl-methyl)-1-pyrrolidinyl)-5-trifluoromethyl-pyrimidine

[1478] HPLC/MS (method B): RT=2.67 min.; [M+H]+=460,1

[1479] (356)2-(3,4-dichlorophenylamino)-4-(3-methoxycarbonylmethyl-1-piperidinyl)-5-trifluoromethyl-pyrimidine

[1480] HPLC/MS (method B): RT=3.59 min.; [M+H]+=463,3

[1481] (357)2-(3,4-dichlorophenylamino)-4-(3-(3-diethylamino-1-propyl)-1-piperidinyl)-5-trifluoromethyl-pyrimidine

[1482] HPLC/MS (method B): RT=2.94 min.; [M+H]+=504,1

[1483] (358)2-(3,4-dichlorophenylamino)-4-(5-hydroxy-2-methyl-2,8-diaza-spiro[5.5]undec-8-yl)-5-trifluoromethyl-pyrimidine

[1484] HPLC/MS (method B): RT=2.6 min.; [M+H]+=490,2

[1485] (359)2-(3,4-dichlorophenylamino)-4-(3-(1-pyrrolidinyl-methyl)-1-piperidinyl)-5-trifluoromethyl-pyrimidine

[1486] HPLC/MS (method B): RT=2.74 min.; [M+H]+=474,1

[1487] (360)2-(3,4-dichlorophenylamino)-4-(3-carboxy-1-piperidinyl)-5-trifluoromethyl-pyrimidine

[1488] HPLC/MS (method B): RT=3.12 min.; [M+H]+=435,2

[1489] (361)2-(3,4-dichlorophenylamino)-4-(2-(2-(2-dimethylamino-1-ethyl)-1-piperidinyl)1-ethylamino)-5-trifluoromethyl-pyrimidine

[1490] HPLC/MS (method B): RT=2.2 min.; [M+H]+=505,2

[1491] (362)2-(3,4-dichlorophenylamino)-4-(3-(2-diethylaminomethyl-1-piperidinyl)-1-propylamino)-5-trifluoromethyl-pyrimidine

[1492] HPLC/MS (method B): RT=2.21 min.; [M+H]+=533,2

[1493] (363)2-(3,4-dichlorophenylamino)-4-(4-(8-methyl-8-aza-bicyclo[3.2.1]oct-3-yl)-1-piperazinyl)-5-trifluoromethyl-pyrimidine

[1494] HPLC/MS (method B): RT=2.16 min.; [M+H]+=515,2

[1495] (364)2-(3,4-dichlorophenylamino)-4-(1-carboxy-2-(4-chlorophenyl)-1-ethyl-amino)-5-trifluoromethyl-pyrimidine

[1496] HPLC/MS (method B): RT=3.14 min.; [M+H]+=505,04

[1497] (365)2-(3,4-dichlorophenylamino)-4-(carboxymethylaminocarbonylmethylamino)-5-trifluoromethyl-pyrimidine

[1498] HPLC/MS (method B): RT=1.8 min.; [M+H]+=438

[1499] (366)2-(3,4-dichlorophenylamino)-4-(carboxy-phenyl-methylamino)-5-trifluoromethyl-pyrimidine

[1500] HPLC/MS (method B): RT=2.85 min.; [M+H]+=457,22

[1501] (367)2-(3,4-dichlorophenylamino)-4-(4′-hydroxy-biphenyl-4-ylmethylamino)-5-trifluoromethyl-pyrimidine

[1502] HPLC/MS (method B): RT=3.28 min.; [M+H]+=505,1

[1503] (368)2-(3,4-dichlorophenylamino)-4-(N-[4-amino-benzyl]-N-[2-methoxy-1-ethyl]-amino)-5-trifluoromethyl-pyrimidine

[1504] HPLC/MS (method B): RT=2.64 min.; [M+H]+=486,0

[1505] (369)2-(3,4-dichlorophenylamino)-4-(4-hydroxy-benzylamino)-5-trifluoromethyl-pyrimidine

[1506] HPLC/MS (method B): RT=2.9 min.; [M+H]+=429,1

[1507] (370)2-(3,4-dichlorophenylamino)-4-(2-diphenylmethoxy-1-ethylamino)-5-trifluoromethyl-pyrimidine

[1508] (371)2-(3,4-dichlorophenylamino)-4-(N-aminocarbonylmethyl-N-methyl-amino)-5-trifluoromethyl-pyrimidine

[1509] HPLC/MS (method B): RT=2.55 min.; [M+H]+=394,1

[1510] (372)2-(3,4-dichlorophenylamino)-4-(2-methylaminocarbonyl-1-ethylamino)-5-trifluoromethyl-pyrimidine

[1511] HPLC/MS (method B): RT=2.5 min.; [M+H]+=408,1

[1512] (373)2-(3,4-dichlorophenylamino)-4-(2-dimethylaminocarbonyl-1-ethylamino)-5-trifluoromethyl-pyrimidine

[1513] HPLC/MS (method B): RT=2.69 min.; [M+H]+=422,1

[1514] (374)2-(3,4-dichlorophenylamino)-4-(2-(4-methyl-1-piperazinyl)-carbonyl1-ethylamino)-5-trifluoromethyl-pyrimidine

[1515] HPLC/MS (method B): RT=2.2 min.; [M+H]+=477,1

[1516] (375)2-(3,4-dichlorophenylamino)-4-(4-carboxy-3-thiazolidinyl)-5-trifluoromethyl-pyrimidine

[1517] HPLC/MS (method B): RT=2.84 min.; [M+H]+=439,11

[1518] (376)2-(3,4-dichlorophenylamino)-4-((R)carboxy-(4-hydroxyphenyl)-methylamino)-5-trifluoromethyl-pyrimidine

[1519] HPLC/MS (method B): RT=2.4 min.; [M+H]+=473,13

[1520] (377)2-(3,4-dichlorophenylamino)-4-(1′-carboxy-5-benzyloxycarbonylamino-1-pentylamino)-5-trifluoromethyl-pyrimidine

[1521] HPLC/MS (method B): RT=2.84 min.; [M+H]+=586,12

[1522] (378)2-(3,4-dichlorophenylamino)-4-(1-(1H-benzimidazol-2-yl)-1-ethylamino)-5-trifluoromethyl-pyrimidine

[1523] HPLC/MS (method B): RT=2.65 min.; [M+H]+=467,1

[1524] (379)2-(3,4-dichlorophenylamino)-4-(4-(4-ethoxycarbonyl-1-piperidinyl)-1-piperidinyl)-5-trifluoromethyl-pyrimidine

[1525] HPLC/MS (method B): RT=2.84 min.; [M+H]+=546,2

[1526] (380)2-(3,4-dichlorophenylamino)-4-(4-(3-hydroxy-1-piperidinyl)-1-piperidinyl)-5-trifluoromethyl-pyrimidine

[1527] HPLC/MS (method B): RT=2.56 min.; [M+H]+=490,2

[1528] (381)2-(3,4-dichlorophenylamino)-4-(N-methyl-N-[2-pyrazinyl-methyl]-amino)-5-trifluoromethyl-pyrimidine

[1529] HPLC/MS (method B): RT=3.06 min.; [M+H]+=429,2

[1530] (382)2-(3,4-dichlorophenylamino)-4-((S)carboxy-(4-hydroxyphenyl)-methylamino)-5-trifluoromethyl-pyrimidine

[1531] HPLC/MS (method B): RT=2.39 min.; [M+H]+=473,33

[1532] (383)2-(3,4-dichlorophenylamino)-4-(1-phenylsulphonyl-4-piperidinylamino)-5-trifluoromethyl-pyrimidine

[1533] (384)2-(3,4-dichlorophenylamino)-4-(4-(4-hydroxyphenyl)-1-butylamino)-5-trifluoromethyl-pyrimidine

[1534] HPLC/MS (method B): RT=3.14 min.; [M+H]+=471,3

[1535] (385) tert-butyl(2-[2-(3,4-dichloro-phenylamino)-5-trifluoromethyl-pyrimidin-4-ylamino]-ethyl)-methyl-carbaminate

[1536] melting point: 140-141° C.

[1537] R_(f)=0,43 (silica gel; methylene chloride:methanol=9:1)

[1538] HPLC/MS (method K): RT=3.58 min.; [M+H]+=481; Abs. λ max=266,5 nm

[1539] (386)2-(3,4-dichlorophenylamino)-4-(4-(3-carboxy-1-propyl)-cyclohexylamino)-5-trifluoromethyl-pyrimidine

[1540] HPLC/MS (method B): RT=2.36 min.; [M+H]+=396,2

[1541] (387)2-(3,4-dichlorophenylamino)-4-(4-(2-carboxy-1-ethyl)-cyclohexylmethylamino)-5-trifluoromethyl-pyrimidine

[1542] HPLC/MS (method B): RT=3.05 min.; [M+H]+=491,3

[1543] (388)2-(3,4-dichlorophenylamino)-4-(1-carboxy-2-propylamino)-5-trifluoromethyl-pyrimidine

[1544] HPLC/MS (method B): RT=2.76 min.; [M+H]+=409,2

[1545] (389)2-(3,4-dichlorophenylamino)-4-(2-(2-hydroxyphenyl)-1-ethylamino)-5-trifluoromethyl-pyrimidine

[1546] HPLC/MS (method B): RT=3.16 min.; [M+H]+=443,2

[1547] (390) tert. butyl(1-[2-(4-carbamoyl-phenylamino)-5-trifluoromethyl-pyrimidin-4-yl]-pyrrolidin-3-yl)-carbaminate

[1548] melting point: 225-228° C.

[1549] R_(f)=0,20 (silica gel; methylene chloride:methanol=9:1)

[1550] HPLC/MS (method G): RT=3.70 min.; [M+H]+=467; Abs. λ max=283,6 nm

[1551] (391)2-(3,4-dichlorophenylamino)-4-(3-carboxy-benzylamino)-5-trifluoromethyl-pyrimidine

[1552] HPLC/MS (method B): RT=2.91 min.; [M+H]+=457,2

[1553] (392)2-(3,4-dichlorophenylamino)-4-(6-tert.-butyloxycarbonylamino-1-hexylamino)-5-trifluoromethyl-pyrimidine

[1554] HPLC/MS (method B): RT=3.47 min.; [M+H]+=522,0

[1555] (393)2-(3,4-dichlorophenylamino)-4-(3-tert.-butyloxycarbonylamino-1-propylamino)-5-trifluoromethyl-pyrimidine

[1556] HPLC/MS (method B): RT=3.28 min.; [M+H]+=480,0

[1557] (394)2-(3,4-dichlorophenylamino)-4-(4-carboxy-1-methyl-4-piperidinylamino)-5-trifluoromethyl-pyrimidine

[1558] HPLC/MS (method B): RT=2.09 min.; [M+H]+=464,1

[1559] (395)2-(3,4-dichlorophenylamino)-4-(1-carboxy-2-(2-chlorophenyl)-1-ethylamino)-5-trifluoromethyl-pyrimidine

[1560] HPLC/MS (method B): RT=2.96 min.; [M+H]+=504,77

[1561] (396)2-(3,4-dichlorophenylamino)-4-(N-benzyl-N-[1-methoxycarbonyl-1-ethyl]-amino)-5-trifluoromethyl-pyrimidine

[1562] (397)2-(3,4-dichlorophenylamino)-4-(N-[ethoxycarbonylmethyl]-N-isopropyl-amino)-5-trifluoromethyl-pyrimidine

[1563] HPLC/MS (method B): RT=3.7 min.; [M+H]+=451

[1564] (398)2-(3,4-dichlorophenylamino)-4-(2-(2-ethoxycarbonyl-1-ethyl)-1-pyrrolidinyl)-5-trifluoromethyl-pyrimidine

[1565] HPLC/MS (method B): RT=3.42 min.; [M+H]+=477,2

[1566] (399)2-(3,4-dichlorophenylamino)-4-(carbamimidoyl-methylamino)-5-trifluoromethyl-pyrimidine

[1567] HPLC/MS (method B): RT=1.74 min.; [M+H]+=379,13

[1568] (400)2-(3,4-dichlorophenylamino)-4-(N-[4-hydroxycyclohexyl]-N-methylamino)-5-trifluoromethyl-pyrimidine

[1569] HPLC/MS (method B): RT=2.86 min.; [M+H]+=435,2

[1570] (401)2-(3,4-dichlorophenylamino)-4-(2-(6-methoxy-1H-benzimidazol-2-yl)-1-ethyl)-5-trifluoromethyl-pyrimidine

[1571] HPLC/MS (method B): RT=2.31 min.; [M+H]+=497,0

[1572] (402)2-(3,4-dichlorophenylamino)-4-(2-carboxy-benzylamino)-5-trifluoromethyl-pyrimidine

[1573] HPLC/MS (method B): RT=2.59 min.; [M+H]+=457,26

[1574] (403)2-(3,4-dichlorophenylamino)-4-(2-aminocarbonyl-1,3-dihydro-isoindol-5-yl-methylamino)-5-trifluoromethyl-pyrimidine

[1575] HPLC/MS (method B): RT=2.68 min.; [M+H]+=497,2

[1576] (404)2-(3,4-dichlorophenylamino)-4-(3-(tert.-butyloxycarbonylaminomethyl)-cyclohexylmethylamino)-5-trifluoromethyl-pyrimidine

[1577] HPLC/MS (method B): RT=3.61 min.; [M+H]+=548,0

[1578] (405)2-(3,4-dichlorophenylamino)-4-(2-methyl-4-phenylaminocarbonylamino-2-butylamino)-5-trifluoromethyl-pyrimidine

[1579] (406)2-(3,4-dichlorophenylamino)-4-(3-dimethylaminocarbonyl-1-piperidinyl)-5-trifluoromethyl-pyrimidine

[1580] HPLC/MS (method B): RT=3.1 min.; [M+H]+=462,2

[1581] (407)2-(3,4-dichlorophenylamino)-4-(2-hydroxy-cyclohexylamino)-5-trifluoromethyl-pyrimidine

[1582] HPLC/MS (method B): RT=2.96 min.; [M+H]+=421,2

[1583] (408)2-(3,4-dichlorophenylamino)-4-(2-hydroxymethyl-1-piperidinyl)-5-trifluoromethyl-pyrimidine

[1584] HPLC/MS (method B): RT=2.62 min.; [M+H]+=421,1

[1585] (409)2-(3,4-dichlorophenylamino)-4-(N-methyl-N-[2-pyridyl-methyl]-amino)-5-trifluoromethyl-pyrimidine

[1586] HPLC/MS (method B): RT=2.48 min.; [M+H]+=428,1

[1587] (410)2-(3,4-dichlorophenylamino)-4-(N-methyl-N-[3-pyridyl-methyl]-amino)-5-trifluoromethyl-pyrimidine

[1588] HPLC/MS (method B): RT=2.91 min.; [M+H]+=443,2

[1589] (411)2-(3,4-dichlorophenylamino)-4-(1-ethyl-3-piperidinylamino)-5-trifluoromethyl-pyrimidine

[1590] HPLC/MS (method B): RT=3.6 min.; [M+H]+=492,2

[1591] (412)2-(3,4-dichlorophenylamino)-4-(2-dimethylamino-cyclohexylamino)-5-trifluoromethyl-pyrimidine

[1592] HPLC/MS (method B): RT=2.74 min.; [M+H]+=506,1

[1593] (413)2-(3,4-dichlorophenylamino)-4-(4-(3-hydroxy-1-propyl)-1-piperidinyl)-5-trifluoromethyl-pyrimidine

[1594] HPLC/MS (method B): RT=2.46 min.; [M+H]+=367,2

[1595] (414)2-(3,4-dichlorophenylamino)-4-(4-(3-hydroxy-1-propyl)-1-piperazinyl)-5-trifluoromethyl-pyrimidine

[1596] HPLC/MS (method B): RT=2.5 min.; [M+H]+=411,2

[1597] (415)2-(3,4-dichlorophenylamino)-4-(N-methyl-N-[3-(4-pyridyl)-1-propyl]-amino)-5-trifluoromethyl-pyrimidine

[1598] HPLC/MS (method B): RT=2.5 min.; [M+H]+=456,1

[1599] (416)2-(3,4-dichlorophenylamino)-4-(4-dimethylamino-2-phenyl-1-butylamino)-5-trifluoromethyl-pyrimidine

[1600] HPLC/MS (method B): RT=2.37 min.; [M+H]+=498,1

[1601] (417)2-(3,4-dichlorophenylamino)-4-(2-(3-diethylamino-1-propyl)-1-piperidinyl)-5-trifluoromethyl-pyrimidine

[1602] HPLC/MS (method B): RT=2.92 min.; [M+H]+=504,1

[1603] (418)2-(3,4-dichlorophenylamino)-4-(bis-[3-pyridylmethyl]-amino)-5-trifluoromethyl-pyrimidine

[1604] HPLC/MS (method B): RT=2.01 min.; [M+H]+=505,2

[1605] (419)2-(3,4-dichlorophenylamino)-4-(4-(N-methyl-N-[2-methoxycarbonyl-1-ethyl]-amino)-1-piperidinyl)-5-trifluoromethyl-pyrimidine

[1606] HPLC/MS (method B): RT=2.23 min.; [M+H]+=506,12

[1607] (420)2-(3,4-dichlorophenylamino)-4-(2-(4-(2H-pyridazin-3-on-6-yl)-phenyl)-1-ethylamino)-1-piperidinyl)-5-trifluoromethyl-pyrimidine

[1608] (421)2-(3,4-dichlorophenylamino)-4-(3-(4-amino-3,5-dichlorophenyl)-1-propylamino)-5-trifluoromethyl-pyrimidine

[1609] HPLC/MS (method B): RT=3.6 min.; [M+H]+=524,0

[1610] (422)2-(3,4-dichlorophenylamino)-4-(4-(2-(N-[dimethylaminocarbonylmethyl]-N-methyl-amino)-1-ethyl-amino)-1-piperidinyl)-5-trifluoromethyl-pyrimidine

[1611] HPLC/MS (method B): RT=2.13 min.; [M+H]+=533,03

[1612] (423)2-(3,4-dichlorophenylamino)-4-(2-(2-(2-diethylamino-1-ethoxy)-1-ethyl)-1-piperidinyl)-5-trifluoromethyl-pyrimidine

[1613] HPLC/MS (method B): RT=3.02 min.; [M+H]+=534,2

[1614] (424)2-(3,4-dichlorophenylamino)-4-(4-(2-(2-diethylamino-1-ethoxy)-1-ethyl)-1-piperidinyl)-5-trifluoromethyl-pyrimidine

[1615] HPLC/MS (method B): RT=2.67 min.; [M+H]+=534,2

[1616] (425)2-(3,4-dichlorophenylamino)-4-(5-(3-carboxy-1-propyl)-indan-2-yl-amino)-5-trifluoromethyl-pyrimidine

[1617] HPLC/MS (method B): RT=3.16 min.; [M+H]+=525,2

[1618] (426)2-(3,4-dichlorophenylamino)-4-(2-ethoxycarbonyl-1-(3-pyridyl)-1-ethyl-amino)-5-trifluoromethyl-pyrimidine

[1619] HPLC/MS (method B): RT=2.78 min.; [M+H]+=500,2

[1620] (427)2-(3,4-dichlorophenylamino)-4-(1,1-dimethyl-3-(2-oxo-3-pyridin-4-yl-imidazolidin-1-yl)-propylamino)-5-trifluoromethyl-pyrimidine

[1621] HPLC/MS (method B): RT=2.05 min.; [M+H]+=554,3

[1622] (428)2-(4-chlorophenylamino)-4-(4-methylpiperazino)-5-nitro-pyrimidinemelting point: 178-180° C.

[1623] (429)2-(4-chlorophenylamino)-4-(4-hydroxy-1-piperidinyl)-5-nitro-pyrimidin

[1624] HPLC/MS (method B): RT=2.76 min.; [M+H]+=350,2

[1625] (430)2-(4-chlorophenylamino)-4-[2-(dimethylamino)-1-ethylamino]-5-nitro-pyrimidinemelting point: 179-181° C.

[1626] (431)2-(4-chlorophenylamino)-4-(3-(4-morpholinyl)-1-propylamino)-5-nitro-pyrimidine

[1627] HPLC/MS (method B): RT=2.23 min.; [M+H]+=393,2

[1628] (432)2-(4-chlorophenylamino)-4-(2-carboxy-1-ethylamino)-5-nitro-pyrimidine

[1629] Prepared from compound 632 of Example 1 by subsequently reactingwith 1N sodiuim hydroxde solution in tetrahydrofuran.

[1630] melting point: >300° C.

[1631] Rf value: 0,40 (silica gel; methylene chloride/methanol=9:1)

[1632] (433)2-(4-chlorophenylamino)-4-(3-(1H-1-imidazolyl)-1-propylamino)-5-nitro-pyrimidine

[1633] HPLC/MS (method B): RT=2.28 min.; [M+H]+=374,2

[1634] (434)2-(4-chlorophenylamino)-4-(3-dimethylamino-1-propylamino)-5-nitro-pyrimidine

[1635] melting point: 148-150° C.

[1636] (435)2-(4-chlorophenylamino)-4-(2-diisopropylamino-1-ethylamino)-5-nitro-pyrimidine

[1637] HPLC/MS (method B): RT=2.4 min.; [M+H]+=393,2

[1638] (436)2-(4-chlorophenylamino)-4-(bis-(2-methoxyethyl)amino)-5-nitro-pyrimidine

[1639] HPLC/MS (method B): RT=3.31 min.; [M+H]+=382,1

[1640] (437)2-(4-chlorophenylamino)-4-(N-methyl-N-(2-methylamino-1-ethyl)-amino)-5-nitro-pyrimidine

[1641] HPLC/MS (method B): RT=2.4 min.; [M+H]+=337,0

[1642] (438)2-(4-chlorophenylamino)-4-(2-(4-pyridyl)-1-ethylamino)-5-nitro-pyrimidine

[1643] HPLC/MS (method B): RT=2.26 min.; [M+H]+=371,1

[1644] (439)2-(4-chlorophenylamino)-4-(4-aminosulphonyl-benzylamino)-5-nitro-pyrimidine

[1645] HPLC/MS (method B): RT=2.89 min.; [M+H]+=435,2

[1646] (440)2-(3,4-dichlorophenylamino)-4-(2-acetylamino-ethylamino)-5-fluor-pyrimidin

[1647] (441)2-(4-chlorophenylamino)-4-(4-pyridyl-methylamino)-5-nitro-pyrimidine

[1648] HPLC/MS (method B): RT=2.15 min.; [M+H]+=357,1

[1649] (442)2-(4-chlorophenylamino)-4-((3-chlor-5-trifluoromethyl-2-pyridyl)-methylamino)-5-nitro-pyrimidine

[1650] HPLC/MS (method B): RT=3.91 min.; [M+H]+=459,1

[1651] (443)2-(4-chlorophenylamino)-4-((4-ethoxycarbonyl-1H-pyrazol-5-yl)-methylamino)-5-nitro-pyrimidine

[1652] (444)2-(4-chlorophenylamino)-4-(3-nitrobenzylamino)-5-nitro-pyrimidine

[1653] HPLC/MS (method B): RT=3.31 min.; [M+H]+=401,2

[1654] (445)2-(4-chlorophenylamino)-4-(4-(2-carboxy-1-ethyl)-1-piperidinyl)-5-nitro-pyrimidine

[1655] HPLC/MS (method B): RT=3.08 min.; [M+H]+=406,2

[1656] (446)2-(4-chlorophenylamino)-4-(3-(1-pyrrolidinyl)-1-propylamino)-5-nitro-pyrimidine

[1657] HPLC/MS (method B): RT=2.31 min.; [M+H]+=377,2

[1658] (447)2-(4-chlorophenylamino)-4-(5-acetylamino-5-methoxycarbonyl-1-pentylamino)-5-nitro-pyrimidine

[1659] HPLC/MS (method B): RT=2.66 min.; [M+H]+=451,2

[1660] (448)2-(4-chlorophenylamino)-4-((1-hydroxy-1-cyclohexyl)-methylamino)-5-nitro-pyrimidine

[1661] HPLC/MS (method B): RT=3.45 min.; [M+H]+=378,2

[1662] (449)2-(4-chlorophenylamino)-4-(2-(1H-indol-3-yl)-1-ethylamino)-5-nitro-pyrimidine

[1663] HPLC/MS (method B): RT=3.64 min.; [M+H]+=409,2

[1664] (450)2-(4-chlorophenylamino)-4-(2-(4-nitro-2-pyridyl-amino)-1-ethylamino)-5-nitro-pyrimidine

[1665] HPLC/MS (method B): RT=3.05 min.; [M+H]+=431,1

[1666] (451)2-(4-chlorophenylamino)-4-(2-hydroxy-2-phenyl-1-ethylamino)-5-nitro-pyrimidine

[1667] HPLC/MS (method B): RT=3.3 min.; [M+H]+=386,3

[1668] (452)2-(4-chlorophenylamino)-4-(2-phenylamino-1-ethylamino)-5-nitro-pyrimidine

[1669] HPLC/MS (method B): RT=3.08 min.; [M+H]+=385,1

[1670] (453)2-(4-chlorophenylamino)-4-(2-(4-hydroxyphenyl)-1-ethylamino)-5-nitro-pyrimidine

[1671] HPLC/MS (method B): RT=3.24 min.; [M+H]+=386,2

[1672] (454)2-(4-chlorophenylamino)-4-(2-(4-aminosulphonylphenyl)-1-ethylamino)-5-nitro-pyrimidine

[1673] HPLC/MS (method B): RT=2.85 min.; [M+H]+=449,1

[1674] (455)2-(4-chlorophenylamino)-4-(2-(1-naphthylamino)-1-ethylamino)-5-nitro-pyrimidine

[1675] HPLC/MS (method B): RT=3.8 min.; [M+H]+=435,2

[1676] (456)2-(4-chlorophenylamino)-4-(2-(4-nitrophenyl)-1-ethylamino)-5-nitro-pyrimidine

[1677] HPLC/MS (method B): RT=3.5 min.; [M+H]+=415,3

[1678] (457)2-(4-chlorophenylamino)-4-(3-ethoxycarbonyl-1-propylamino)-5-nitro-pyrimidinemelting point: 133-135° C.

[1679] (458)2-(4-chlorophenylamino)-4-(aminocarbonylmethylamino)-5-nitro-pyrimidine

[1680] HPLC/MS (method B): RT=2.36 min.; [M+H]+=323,1

[1681] (459)4-[4-{3-Amino-pyrrolidin-1-yl)-5-trifluoromethyl-pyrimidin-2-ylamino)-benzamide

[1682] Prepared analogously to 1(80).

[1683] R_(f)=0,13 (silica gel; methylene chloride:methanol=4:1)

[1684] HPLC/MS (method G): RT=2.59 min.; [M+H]+=367; Abs. λ max=281,7 nm

[1685] (460)2-(4-chlorophenylamino)-4-(2-tert.-butyloxycarbonylamino-1-ethylamino)-5-nitro-pyrimidine

[1686] HPLC/MS (method B): RT=3.24 min.; [M+H]+=409,1

[1687] (461)2-(4-chlorophenylamino)-4-(1-ethyl-2-pyrrolidinyl-methylamino)-5-nitro-pyrimidine

[1688] HPLC/MS (method B): RT=2.28 min.; [M+H]+=377,2

[1689] (462)2-(4-chlorophenylamino)-4-(2-(1-pyrrolidinyl)-1-ethylamino)-5-nitro-pyrimidine

[1690] HPLC/MS (method B): RT=2.25 min.; [M+H]+=363,2

[1691] (463)2-(4-chlorophenylamino)-4-(2-tetrahydrofuryl-methylamino)-5-nitro-pyrimidine

[1692] (464)2-(4-chlorophenylamino)-4-(2-(1-piperidinyl)-1-ethylamino)-5-nitro-pyrimidine

[1693] HPLC/MS (method B): RT=2.3 min.; [M+H]+=377,1

[1694] (465)2-(4-chlorophenylamino)-4-(2-hydroxy-1-propylamino)-5-nitro-pyrimidine

[1695] HPLC/MS (method B): RT=2.85 min.; [M+H]+=324,2

[1696] (466)2-(4-chlorophenylamino)-4-(2,3-dihydroxy-1-propylamino)-5-nitro-pyrimidine

[1697] HPLC/MS (method B): RT=2.41 min.; [M+H]+=340,2

[1698] (467)2-(4-chlorophenylamino)-4-(2-diethylamino-1-ethylamino)-5-nitro-pyrimidine

[1699] HPLC/MS (method B): RT=2.27 min.; [M+H]+=365,2

[1700] (468)2-(4-chlorophenylamino)-4-(2-(2-hydroxyethoxy)-1-ethylamino)-5-nitro-pyrimidine

[1701] HPLC/MS (method B): RT=2.71 min.; [M+H]+=354,2

[1702] (469)2-(4-chlorophenylamino)-4-(2-hydroxy-1-ethylamino)-5-nitro-pyrimidinemelting point: 226-228° C.

[1703] (470)2-(4-chlorophenylamino)-4-(3-diethylamino-1-propylamino)-5-nitro-pyrimidine

[1704] HPLC/MS (method B): RT=2.35 min.; [M+H]+=379,2

[1705] (471)2-(4-chlorophenylamino)-4-(3-hydroxy-1-propylamino)-5-nitro-pyrimidinemelting point: 190-194° C.

[1706] (472)2-(4-chlorophenylamino)-4-(2-(1-methyl-1H-pyrrol-2-yl)-1-ethylamino)-5-nitro-pyrimidine

[1707] HPLC/MS (method B): RT=3.41 min.; [M+H]+=373,2

[1708] (473)2-(4-chlorophenylamino)-4-(4-hydroxy-3-methoxy-benzylamino)-5-nitro-pyrimidine

[1709] HPLC/MS (method B): RT=3.15 min.; [M+H]+=402,1

[1710] (474)2-(4-chlorophenylamino)-4-(2-methylsulphanyl-1-ethylamino)-5-nitro-pyrimidine

[1711] HPLC/MS (method B): RT=3.46 min.; [M+H]+=340,1

[1712] (475)2-(4-chlorophenylamino)-4-(3-methoxy-1-propylamino)-5-nitro-pyrimidinemelting point: 148-150° C.

[1713] (476)2-(4-chlorophenylamino)-4-(2,2-dimethyl-3-dimethylamino-1-propylamino)-5-nitro-pyrimidine

[1714] HPLC/MS (method B): RT=2.4 min.; [M+H]+=379,2

[1715] (477)2-(4-chlorophenylamino)-4-(2,2-dimethyl-3-hydroxy-1-propylamino)-5-nitro-pyrimidine

[1716] HPLC/MS (method B): RT=3.17 min.; [M+H]+=352,2

[1717] (478)2-(4-chlorophenylamino)-4-cyanomethylamino-5-nitro-pyrimidine

[1718] HPLC/MS (method B): RT=2.49 min.; [M+H]+=305,14

[1719] (479)2-(4-chlorophenylamino)-4-(3-aminocarbonyl-1-piperidinyl)-5-nitro-pyrimidine

[1720] HPLC/MS (method B): RT=2.69 min.; [M+H]+=377,2

[1721] (480)2-(4-chlorophenylamino)-4-(4-acetyl-1-piperazinyl)-5-nitro-pyrimidine

[1722] HPLC/MS (method B): RT=3.64 min.; [M+H]+=409,2

[1723] (481)2-(4-chlorophenylamino)-4-(4-(1-piperidinyl)-1-piperidinyl)-5-nitro-pyrimidine

[1724] HPLC/MS (method B): RT=2.31 min.; [M+H]+=377,2

[1725] (482)2-(4-chlorophenylamino)-4-(4-(morpholinocarbonylmethyl)-1-piperazinyl)-5-nitro-pyrimidine

[1726] HPLC/MS (method B): RT=2.28 min.; [M+H]+=462,2

[1727] (483) 2-(4-chlorophenylamino)-4-piperazino-5-nitro-pyrimidine

[1728] Rf value: 0,20 (silica gel; methylene chloride/methanol/conc.aqueous ammonia=9:1:0,1)

[1729] (484)2-(4-chlorophenylamino)-4-(3-[4-(3-amino-1-propyl)-1-piperazinyl]-1-propylamino)-5-nitro-pyrimidine

[1730] HPLC/MS (method B): RT=2.41 min.; [M+H]+=519,2

[1731] (485)2-(4-chlorophenylamino)-4-(cis-4-carboxy-cyclohexylamino)-5-nitro-pyrimidine

[1732] HPLC/MS (method B): RT=2.38 min.; [M+H]+=392,0

[1733] (486)2-(4-chlorophenylamino)-4-(3-dibenzylamino-1-propylamino)-5-nitro-pyrimidine

[1734] HPLC/MS (method B): RT=2.65 min.; [M+H]+=560,1

[1735] (487)2-(4-chlorophenylamino)-4-(N-[4-methoxycarbonyl-cyclohexyl]-N-[3-pyridylmethyl]amino)-5-nitro-pyrimidine

[1736] (488)2-(3,4-dichlorophenylamino)-4-(2-acetylamino-ethylamino)-5-dimethylaminomethyl-pyrimidine

[1737] (489)2-(4-chlorophenylamino)-4-(2-phenyl-1-(4-phenyl-1-butyl-aminocarbonyl)-1-ethylamino)-5-nitro-pyrimidine

[1738] HPLC/MS (method B): RT=3.6 min.; [M+H]+=545

[1739] (490)2-(4-chlorophenylamino)-4-(1-aminocarbonyl-2-(4-methoxyphenyl)-1-ethylamino)-5-nitro-pyrimidine

[1740] HPLC/MS (method B): RT=2.66 min.; [M+H]+=443,2

[1741] (491)2-(4-chlorophenylamino)-4-(1-dimethylaminomethylcarbonyl-4-piperidinyl-methylamino)-5-nitro-pyrimidine

[1742] (492)2-(4-chlorophenylamino)-4-(N-ethyl-N-[4-pyridylmethyl]amino)-5-nitro-pyrimidine

[1743] HPLC/MS (method B): RT=2.38 min.; [M+H]+=385,1

[1744] (493)2-(4-chlorophenylamino)-4-(3-phenyl-azepan-4-on-1-yl)-5-nitro-pyrimidine

[1745] (494)2-(4-chlorophenylamino)-4-(2-(3-hydroxy-1-propyl)-1-piperidinyl)-5-nitro-pyrimidine

[1746] HPLC/MS (method B): RT=3.17 min.; [M+H]+=392,3

[1747] (495)2-(4-chlorophenylamino)-4-(4-(8-methoxy-3,4-dihydro-1H-quinazolin-2-on-3-yl)-1-piperidinyl)-5-nitro-pyrimidine

[1748] HPLC/MS (method B): RT=3.03 min.; [M+H]+=510,1

[1749] (496)2-(4-chlorophenylamino)-4-(4-(2-nitrophenyl)-1-piperazinyl)-5-nitro-pyrimidine

[1750] HPLC/MS (method B): RT=3.6 min.; [M+H]+=456,0

[1751] (497)2-(4-chlorophenylamino)-4-(4-(3,4-dimethoxyphenyl)-1-piperazinyl)-5-nitro-pyrimidine

[1752] HPLC/MS (method B): RT=2.34 min.; [M+H]+=396,2

[1753] (498)2-(4-chlorophenylamino)-4-(4-(4-cyanophenyl)-1-piperazinyl)-5-nitro-pyrimidine

[1754] HPLC/MS (method B): RT=3.62 min.; [M+H]+=436,2

[1755] (499)2-(4-chlorophenylamino)-4-(1-benzyl-3-pyrrolidinyl-amino)-5-nitro-pyrimidineHPLCIMS (method B): RT=2.58 min.; [M+H]+=425,3

[1756] (500)2-(4-chlorophenylamino)-4-(1-hydroxy-2-propylamino)-5-nitro-pyrimidine

[1757] HPLC/MS (method B): RT=2.74 min.; [M+H]+=324,2

[1758] (501)2-(4-chlorophenylamino)-4-(3-(1-piperidinyl)-1-propylamino)-5-nitro-pyrimidine

[1759] HPLC/MS (method B): RT=2.36 min.; [M+H]+=391,2

[1760] (502)2-(4-chlorophenylamino)-4-(1-benzyl-4-piperidinyl-amino)-5-nitro-pyrimidine

[1761] HPLC/MS (method B): RT=2.47 min.; [M+H]+=439,2

[1762] (503)2-(4-chlorophenylamino)-4-(4-aminomethyl-benzylamino)-5-nitro-pyrimidine

[1763] HPLC/MS (method B): RT=2.39 min.; [M+H]+=385,1

[1764] (504)2-(4-chlorophenylamino)-4-(4-aminobutylamino)-5-nitro-pyrimidine

[1765] HPLC/MS (method B): RT=2.24 min.; [M+H]+=337,1

[1766] (505)2-(4-chlorophenylamino)-4-(3-amino-2,2-dimethyl-1-propylamino)-5-nitro-pyrimidine

[1767] HPLC/MS (method B): RT=2.35 min.; [M+H]+=351,1

[1768] (506)2-(4-chlorophenylamino)-4-(trans-2-amino-cyclohexylamino)-5-nitro-pyrimidine

[1769] HPLC/MS (method B): RT=2.5 min.; [M+H]+=363,2

[1770] (507)2-(4-chlorophenylamino)-4-(2-(2-(2-amino-1-ethoxy)-1-ethoxy)-1-ethylamino)-5-nitro-pyrimidine

[1771] HPLC/MS (method B): RT=2.13 min.; [M+H]+=397,2

[1772] (508)2-(4-chlorophenylamino)-4-(3-amino-benzylamino)-5-nitro-pyrimidine

[1773] HPLC/MS (method B): RT=2.26 min.; [M+H]+=371,1

[1774] (509)2-(4-chlorophenylamino)-4-(3-amino-2-hydroxy-1-propylamino)-5-nitro-pyrimidine

[1775] (510)2-(4-chlorophenylamino)-4-(2-(2-amino-1-ethylsulphanyl)-1-ethylamino)-5-nitro-pyrimidine

[1776] HPLC/MS (method B): RT=2.34 min.; [M+H]+=369,0

[1777] (511)2-(4-chlorophenylamino)-4-(N-[2-dimethylamino-1-ethyl]-N-ethyl-amino)-5-nitro-pyrimidine

[1778] HPLC/MS (method B): RT=2.4 min.; [M+H]+=365,0

[1779] (512)2-(4-chlorophenylamino)-4-(N-[3-dimethylamino-1-propyl]-N-methyl-amino)-5-nitro-pyrimidine

[1780] HPLC/MS (method B): RT=2.25 min.; [M+H]+=365,1

[1781] (513)2-(4-chlorophenylamino)-4-(3-(4-methyl-1-piperazinyl)-1-propylamino)-5-nitro-pyrimidine

[1782] HPLC/MS (method B): RT=1.84 min.; [M+H]+=406,2

[1783] (514)2-(4-chlorophenylamino)-4-(N-[2-cyano-1-ethyl]-N-[3-pyridylmethyl]-amino)-5-nitro-pyrimidine

[1784] HPLC/MS (method B): RT=2.38 min.; [M+H]+=410,2

[1785] (515)2-(4-chlorophenylamino)-4-(4-(2-pyridyl)-1-piperazinyl)-5-nitro-pyrimidine

[1786] HPLC/MS (method B): RT=2.28 min.; [M+H]+=412,1

[1787] (516)2-(4-chlorophenylamino)-4-(4-[bis-(4-methoxy-phenyl)]-methyl-1-piperazinyl)-5-nitro-pyrimidine

[1788] (517)2-(4-chlorophenylamino)-4-(4-(3-methoxy-phenyl)-1-piperazinyl)-5-nitro-pyrimidine

[1789] HPLC/MS (method B): RT=3.51 min.; [M+H]+=441,2

[1790] (518)2-(4-chlorophenylamino)-4-(N-benzyl-N-[2-cyano-1-ethyl]-amino)-5-nitro-pyrimidine

[1791] HPLC/MS (method B): RT=3.53 min.; [M+H]+=409,2

[1792] (519)2-(4-chlorophenylamino)-4-(N-benzyl-N-[2-hydroxy-1-ethyl]-amino)-5-nitro-pyrimidine

[1793] HPLC/MS (method B): RT=3.27 min.; [M+H]+=400,2

[1794] (520)2-(4-chlorophenylamino)-4-(3-carboxy-1-propyl-amino)-5-nitro-pyrimidine

[1795] Prepared from compound 457 of Example 1 by subsequently reactingwith 1N sodium hydroxide solution in tetrahydrofuran.

[1796] melting point: 258-260° C.

[1797] (521)2-(4-chlorophenylamino)-4-(N-benzyl-N-[ethoxycarbonylmethyl]-amino)-5-nitro-pyrimidine

[1798] HPLC/MS (method B): RT=3.76 min.; [M+H]+=442,2

[1799] (522)2-(4-chlorophenylamino)-4-(N-[4-nitrobenzyl]-N-propyl-amino)-5-nitro-pyrimidine

[1800] HPLC/MS (method B): RT=3.87 min.; [M+H]+=443,2

[1801] (523)2-(4-chlorophenylamino)-4-(cyano-phenyl-methylamino)-5-nitro-pyrimidine

[1802] HPLC/MS (method B): RT=3.91 min.; [M+H]+=459,1

[1803] (524)2-(4-chlorophenylamino)-4-(N-benzyl-N-[4-hydroxy-1-butyl]-amino)-5-nitro-pyrimidine

[1804] HPLC/MS (method B): RT=3.45 min.; [M+H]+=378,2

[1805] (525)2-(4-chlorophenylamino)-4-(N-benzyl-N-[2-hydroxymethyl-1-cyclohexyl]-amino)-5-nitro-pyrimidine

[1806] HPLC/MS (method B): RT=2.45 min.; [M+H]+=468,33

[1807] (526)2-(4-chlorophenylamino)-4-(1-carboxy-2-(4-hydroxyphenyl)-1-ethyl-amino)-5-nitro-pyrimidine

[1808] HPLC/MS (method B): RT=2.43 min.; [M+H]+=430,24

[1809] (527)2-(4-chlorophenylamino)-4-((1S)-1-carboxy-2-hydroxy-1-ethyl-amino)-5-nitro-pyrimidine

[1810] (528)2-(4-chlorophenylamino)-4-(5-carboxy-1-pentyl-amino)-5-nitro-pyrimidine

[1811] HPLC/MS (method B): RT=3 min.; [M+H]+=380,0

[1812] (529)2-(4-chlorophenylamino)-4-(1-carboxy-2-aminocarbonyl-1-ethyl-amino)-5-nitro-pyrimidine

[1813] HPLC/MS (method B): RT=1.88 min.; [M+H]+=381,15

[1814] (530)2-(4-chlorophenylamino)-4-(2-carboxy-2-propyl-amino)-5-nitro-pyrimidine

[1815] HPLC/MS (method B): RT=2.59 min.; [M+H]+=352,2

[1816] (531)2-(4-chlorophenylamino)-4-(1-carboxy-3-methyl-1-propylamino)-5-nitro-pyrimidine

[1817] HPLC/MS (method B): RT=2.8 min.; [M+H]+=366,19

[1818] (532)2-(4-chlorophenylamino)-4-((1R)-1-carboxy-2-hydroxy-1-ethyl-amino)-5-nitro-pyrimidine

[1819] HPLC/MS (method B): RT=2.03 min.; [M+H]+=354,19

[1820] (533)2-(4-chlorophenylamino)-4-(4-(2-amino-1-ethyl)-1-piperazinyl)-5-nitro-pyrimidine

[1821] (534)2-(4-chlorophenylamino)-4-(3,5-dimethyl-1-piperazinyl)-5-nitro-pyrimidine

[1822] HPLC/MS (method B): RT=2.28 min.; [M+H]+=363,2

[1823] (535)2-(4-chlorophenylamino)-4-(cis-2-amino-cyclohexylamino)-5-nitro-pyrimidine

[1824] HPLC/MS (method B): RT=2.51 min.; [M+H]+=363,2

[1825] (536)2-(4-chlorophenylamino)-4-(N-methyl-N-[3-methylamino-1-propyl]-amino)-5-nitro-pyrimidine

[1826] (537)2-(4-chlorophenylamino)-4-(3-hydroxy-8-aza-bicyclo[3.2.1]oct-8-yl)-5-nitro-pyrimidine

[1827] HPLC/MS (method B): RT=3.04 min.; [M+H]+=376,2

[1828] (538)2-(4-chlorophenylamino)-4-(3-amino-1-pyrrolidinyl)-5-nitro-pyrimidine

[1829] HPLC/MS (method B): RT=2.16 min.; [M+H]+=335,1

[1830] (539)2-(4-chlorophenylamino)-4-(4-benzyloxycarbonyl-1-piperazinyl)-5-nitro-pyrimidine

[1831] HPLC/MS (method B): RT=3.57 min.; [M+H]+=469,2

[1832] (540)2-(4-chlorophenylamino)-4-(3-(2-(3-amino-1-propoxy)-1-ethoxy)-1-propylamino)-5-nitro-pyrimidine

[1833] HPLC/MS (method B): RT=2.46 min.; [M+H]+=425,2

[1834] (541)2-(4-chlorophenylamino)-4-(N-benzyl-N-[2-hydroxy-1-phenyl-1-ethyl]-amino)-5-nitro-pyrimidine

[1835] HPLC/MS (method B): RT=3.66 min.; [M+H]+=476,1

[1836] (542)2-(4-chlorophenylamino)-4-(1-homopiperazinyl)-5-nitro-pyrimidine

[1837] HPLC/MS (method B): RT=2.22 min.; [M+H]+=349,1

[1838] (543)2-(4-chlorophenylamino)-4-(2-(2-(2-hydroxy-1-ethoxy)-1-ethoxy)-1-ethylamino)-5-nitro-pyrimidine

[1839] HPLC/MS (method B): RT=2.73 min.; [M+H]+=398,2

[1840] (544)2-(4-chlorophenylamino)-4-(2-(3-methoxycarbonylphenyl)-1-ethyl-amino)-5-nitro-pyrimidine

[1841] HPLC/MS (method B): RT=3.58 min.; [M+H]+=428,2

[1842] (545)2-(4-chlorophenylamino)-4-(2-hydroxy-3-(4-morpholinyl)-1-propyl-amino)-5-nitro-pyrimidine

[1843] HPLC/MS (method B): RT=2.14 min.; [M+H]+=409,2

[1844] (546)2-(4-chlorophenylamino)-4-(N-methyl-N-[2-nitrobenzyl]-amino)-5-nitro-pyrimidine

[1845] (547)2-(4-chlorophenylamino)-4-(2-carboxy-1-phenyl-1-ethyl-amino)-5-nitro-pyrimidine

[1846] (548)2-(4-chlorophenylamino)-4-(N-methyl-N-[6-[N-methyl-N-(2-phenyl-1-ethyl)-amino]-1-hexyl]-amino)-5-nitro-pyrimidine

[1847] HPLC/MS (method B): RT=2.95 min.; [M+H]+=497,4

[1848] (549)2-(4-chlorophenylamino)-4-(2-(2-(2-amino-1-ethyl)-phenyl)-1-ethyl-amino)-5-nitro-pyrimidine

[1849] HPLC/MS (method B): RT=2.65 min.; [M+H]+=413,2

[1850] (550)2-(4-chlorophenylamino)-4-(N-[2-diethylamino-1-ethyl]-N-ethyl-amino)-5-nitro-pyrimidine

[1851] HPLC/MS (method B): RT=2.51 min.; [M+H]+=393,1

[1852] (551)2-(4-chlorophenylamino)-4-(2-ethoxycarbonyl-1-piperidinyl)-5-nitro-pyrimidine

[1853] HPLC/MS (method B): RT=3.81 min.; [M+H]+=406,2

[1854] (552)2-(4-chlorophenylamino)-4-(4-methyl-1-homopiperazinyl)-5-nitro-pyrimidine

[1855] HPLC/MS (method B): RT=2.26 min.; [M+H]+=363,2

[1856] (553)2-(4-chlorophenylamino)-4-(N-cyanomethyl-N-butyl-amino)-5-nitro-pyrimidine

[1857] HPLC/MS (method B): RT=3.52 min.; [M+H]+=361,1

[1858] (554)2-(4-chlorophenylamino)-4-(N-[2-dimethylamino-1-ethyl]-N-methyl-amino)-5-nitro-pyrimidine

[1859] HPLC/MS (method B): RT=2.21 min.; [M+H]+=351,1

[1860] (555)2-(4-chlorophenylamino)-4-(2-(1-pyrrolidinyl-methyl)-1-pyrrolidinyl)-5-nitro-pyrimidineHPLC/MS (method B): RT=2.41 min.; [M+H]+=403,2

[1861] (556)2-(4-chlorophenylamino)-4-(3-methoxycarbonylmethyl-1-piperidinyl)-5-nitro-pyrimidine

[1862] HPLC/MS (method B): RT=3.47 min.; [M+H]+=406,2

[1863] (557)2-(4-chlorophenylamino)-4-(3-(3-diethylamino-1-propyl)-1-piperidinyl)-5-nitro-pyrimidine

[1864] HPLC/MS (method B): RT=2.75 min.; [M+H]+=447,4

[1865] (558)2-(4-chlorophenylamino)-4-(5-hydroxy-2-methyl-2,8-diaza-spiro[5.5]undec-8-yl)-5-nitro-pyrimidine

[1866] HPLC/MS (method B): RT=2.26 min.; [M+H]+=433,2

[1867] (559)2-(4-chlorophenylamino)-4-(3-(1-pyrrolidinyl-methyl)-1-piperidinyl)-5-nitro-pyrimidine

[1868] HPLC/MS (method B): RT=2.5 min.; [M+H]+=417,2

[1869] (560)2-(4-chlorophenylamino)-4-(3-carboxy-1-piperidinyl)-5-nitro-pyrimidine

[1870] HPLC/MS (method B): RT=2.83 min.; [M+H]+=378,2

[1871] (561)2-(4-chlorophenylamino)-4-(2-(2-(2-dimethylamino-1-ethyl)-1-piperidinyl)-1-ethylamino)-5-nitro-pyrimidine

[1872] HPLC/MS (method B): RT=1.82 min.; [M+H]+=448,2

[1873] (562)2-(4-chlorophenylamino)-4-(3-(2-diethylaminomethyl-1-piperidinyl)-1-propylamino)-5-nitro-pyrimidine

[1874] HPLC/MS (method B): RT=1.97 min.; [M+H]+=476,2

[1875] (563)2-(4-chlorophenylamino)-4-(4-(8-methyl-8-aza-bicyclo[3.2.1]oct-3-yl)-1-piperazinyl)-5-nitro-pyrimidine

[1876] HPLC/MS (method B): RT=2.04 min.; [M+H]+=458,3

[1877] (564)2-(4-chlorophenylamino)-4-(1-carboxy-2-(4-chlorophenyl)-1-ethyl-amino)-5-nitro-pyrimidine

[1878] HPLC/MS (method B): RT=3.13 min.; [M+H]+=448,25

[1879] (565)2-(4-chlorophenylamino)-4-(carboxymethylaminocarbonylmethylamino)-5-nitro-pyrimidine

[1880] HPLC/MS (method B): RT=1.93 min.; [M+H]+=381,29

[1881] (566)2-(4-chlorophenylamino)-4-(carboxy-phenyl-methylamino)-5-nitro-pyrimidine

[1882] HPLC/MS (method B): RT=2.87 min.; [M+H]+=400,2

[1883] (567)2-(4-chlorophenylamino)-4-(4′-hydroxy-biphenyl-4-ylmethylamino)-5-nitro-pyrimidine

[1884] HPLC/MS (method B): RT=3.4 min.; [M+H]+=448,1

[1885] (568)2-(4-chlorophenylamino)-4-(N-[4-amino-benzyl]-N-[2-methoxy-1-ethyl]-amino)-5-nitro-pyrimidine

[1886] (569)2-(4-chlorophenylamino)-4-(4-hydroxy-benzylamino)-5-nitro-pyrimidine

[1887] HPLC/MS (method B): RT=3.01 min.; [M+H]+=372,1

[1888] (570)2-(4-chlorophenylamino)-4-(2-diphenylmethoxy-1-ethylamino)-5-nitro-pyrimidine

[1889] (571)2-(4-chlorophenylamino)-4-(N-aminocarbonylmethyl-N-methyl-amino)-5-nitro-pyrimidine

[1890] (572)2-(4-chlorophenylamino)-4-(2-methylaminocarbonyl-1-ethylamino)-5-nitro-pyrimidine

[1891] (573)2-(4-chlorophenylamino)-4-(2-dimethylaminocarbonyl-1-ethylamino)-5-nitro-pyrimidine

[1892] (574)2-(4-chlorophenylamino)-4-(2-(4-methyl-1-piperazinyl)-carbonyl-1-ethylamino)-5-nitro-pyrimidine

[1893] (575)2-(4-chlorophenylamino)-4-(4-carboxy-3-thiazolidinyl)-5-nitro-pyrimidine

[1894] HPLC/MS (method B): RT=2.6 min.; [M+H]+=382

[1895] (576)2-(4-chlorophenylamino)-4-((R)carboxy-(4-hydroxyphenyl)-methylamino)-5-nitro-pyrimidine

[1896] HPLC/MS (method B): RT=2.44 min.; [M+H]+=416,2

[1897] (577)2-(4-chlorophenylamino)-4-(1-carboxy-5-benzyloxycarbonylamino-1-pentylamino)-5-nitro-pyrimidine

[1898] HPLC/MS (method B): RT=3.01 min.; [M+H]+=529,14

[1899] (578)2-(4-chlorophenylamino)-4-(1-(1H-benzimidazol-2-yl)-1-ethylamino)-5-nitro-pyrimidine

[1900] HPLC/MS (method B): RT=2.21 min.; [M+H]+=410,1

[1901] (579)2-(4-chlorophenylamino)-4-(4-(4-ethoxycarbonyl-1-piperidinyl)-1-piperidinyl)-5-nitro-pyrimidine

[1902] HPLC/MS (method B): RT=2.6 min.; [M+H]+=489,3

[1903] (580)2-(4-chlorophenylamino)-4-(4-(3-hydroxy-1-piperidinyl)-1-piperidinyl)-5-nitro-pyrimidine

[1904] HPLC/MS (method B): RT=2.31 min.; [M+H]+=433,3

[1905] (581)2-(4-chlorophenylamino)-4-(N-methyl-N-[2-pyrazinyl-methyl]-amino)-5-nitro-pyrimidine

[1906] HPLC/MS (method B): RT=2.91 min.; [M+H]+=372,1

[1907] (582)2-(4-chlorophenylamino)-4-((S)carboxy-(4-hydroxyphenyl)-methylamino)-5-nitro-pyrimidine

[1908] HPLC/MS (method B): RT=2.47 min.; [M+H]+=416,09

[1909] (583)2-(4-chlorophenylamino)-4-(1-phenylsulphonyl-4-piperidinylamino)-5-nitro-pyrimidine

[1910] (584)2-(4-chlorophenylamino)-4-(4-(4-hydroxyphenyl)-1-butylamino)-5-nitro-pyrimidine

[1911] HPLC/MS (method B): RT=3.38 min.; [M+H]+=414,3

[1912] (585)N-(2-Methyl-2-{2-[4-(morpholin-4-sulphonyl)-phenylamino]-5-trifluoromethyl-pyrimidin-4-ylamino}-propyl)-acetamidemelting point: 69-70° C.

[1913] Rf value: 0,39 (silica gel; ethyl acetate)

[1914] HPLC/MS (method D): RT=5.86 min.; [M+H]+=517; Abs./max 302 nm

[1915] (586)2-(4-chlorophenylamino)-4-(4-(3-carboxy-1-propyl)-cyclohexylamino)-5-nitro-pyrimidine

[1916] (587)2-(4-chlorophenylamino)-4-(4-(2-carboxy-1-ethyl)-cyclohexylmethylamino)-5-nitro-pyrimidine

[1917] HPLC/MS (method B): RT=3.41 min.; [M+H]+=434,3

[1918] (588)2-(4-chlorophenylamino)-4-(1-carboxy-2-propylamino)-5-nitro-pyrimidine

[1919] HPLC/MS (method B): RT=2.95 min.; [M+H]+=352,2

[1920] (589)2-(4-chlorophenylamino)-4-(2-(2-hydroxyphenyl)-1-ethylamino)-5-nitro-pyrimidine

[1921] (590) tert. butyl(2-[2-(4-carbamoyl-phenylamino)-5-trifluoromethyl-pyrimidin-4-ylamino]-ethyl)-3-yl)-methyl-carbaminate

[1922] melting point: 186-187° C.

[1923] R_(f)=0,24 (silica gel; methylene chloride:methanol=9:1)

[1924] HPLC/MS (method G): RT=3.58 min.; [M+H]+=455; Abs. % max=279,8 nm

[1925] (591)2-(4-chlorophenylamino)-4-(3-carboxy-benzylamino)-5-nitro-pyrimidine

[1926] HPLC/MS (method B): RT=3.06 min.; [M+H]+=400,2

[1927] (592)2-(4-chlorophenylamino)-4-(6-tert.-butyloxycarbonylamino-1-hexylamino)-5-nitro-pyrimidine

[1928] HPLC/MS (method B): RT=3.74 min.; [M+H]+=465,0

[1929] (593)2-(4-chlorophenylamino)-4-(3-tert.-butyloxycarbonylamino-1-propylamino)-5-nitro-pyrimidine

[1930] HPLC/MS (method B): RT=3.41 min.; [M+H]+=423,0

[1931] (594)2-(4-chlorophenylamino)-4-(4-carboxy-1-methyl-4-piperidinylamino)-5-nitro-pyrimidine

[1932] HPLC/MS (method B): RT=1.67 min.; [M+H]+=407,3

[1933] (595)2-(4-chlorophenylamino)-4-(1-carboxy-2-(2-chlorophenyl)-1-ethylamino)-5-nitro-pyrimidine

[1934] HPLC/MS (method B): RT=3.1 min.; [M+H]+=448,18

[1935] (596)2-(4-chlorophenylamino)-4-(N-benzyl-N-[1-methoxycarbonyl-1-ethyl]-amino)-5-nitro-pyrimidine

[1936] HPLC/MS (method B): RT=3.72 min.; [M+H]+=442,2

[1937] (597)2-(4-chlorophenylamino)-4-(N-[ethoxycarbonylmethyl]-N-isopropyl-amino)-5-nitro-pyrimidine

[1938] HPLC/MS (method B): RT=3.53 min.; [M+H]+=394,1

[1939] (598)2-(4-chlorophenylamino)-4-(2-(2-ethoxycarbonyl-1-ethyl)-1-pyrrolidinyl)-5-nitro-pyrimidine

[1940] (599)2-(4-chlorophenylamino)-4-(carbamimidoyl-methylamino)-5-nitro-pyrimidine

[1941] HPLC/MS (method B): RT=1.51 min.; [M+H]+=322,22

[1942] (600)2-(4-chlorophenylamino)-4-(N-[4-hydroxycyclohexyl]-N-methylamino)-5-nitro-pyrimidine

[1943] (601)2-(4-chlorophenylamino)-4-(2-(6-methoxy-1H-benzimidazol-2-yl)-1-ethyl)-5-nitro-pyrimidine

[1944] HPLC/MS (method B): RT=2.31 min.; [M+H]+=440,1

[1945] (602)2-(4-chlorophenylamino)-4-(2-carboxy-benzylamino)-5-nitro-pyrimidine

[1946] HPLC/MS (method B): RT=2.88 min.; [M+H]+=400,25

[1947] (603)2-(4-chlorophenylamino)-4-(2-aminocarbonyl-1,3-dihydro-isoindol-5-yl-methylamino)-5-nitro-pyrimidine

[1948] HPLC/MS (method B): RT=2.84 min.; [M+H]+=440,2

[1949] (604)2-(4-chlorophenylamino)-4-(3-(tert.-butyloxycarbonylaminomethyl)-cyclohexylmethylamino)-5-nitro-pyrimidine

[1950] HPLC/MS (method B): RT=3.97 min.; [M+H]+=491,0

[1951] (605)2-(4-chlorophenylamino)-4-(2-methyl-4-phenylaminocarbonylamino-2-butylamino)-5-nitro-pyrimidine

[1952] HPLC/MS (method B): RT=3.18 min.; [M+H]+=470,1

[1953] (606)2-(4-chlorophenylamino)-4-(3-dimethylaminocarbonyl-1-piperidinyl)-5-nitro-pyrimidine

[1954] HPLC/MS (method B): RT=2.99 min.; [M+H]+=405,2

[1955] (607)2-(4-chlorophenylamino)-4-(2-hydroxy-cyclohexylamino)-5-nitro-pyrimidine

[1956] HPLC/MS (method B): RT=2.2 min.; [M+H]+=382,1

[1957] (608)2-(4-chlorophenylamino)-4-(2-hydroxymethyl-1-piperidinyl)-5-nitro-pyrimidine

[1958] HPLC/MS (method B): RT=3.08 min.; [M+H]+=364,2

[1959] (609)2-(4-chlorophenylamino)-4-(N-methyl-N-[2-pyridyl-methyl]-amino)-5-nitro-pyrimidine

[1960] HPLC/MS (method B): RT=2.34 min.; [M+H]+=371,1

[1961] (610)2-(4-chlorophenylamino)-4-(N-methyl-N-[3-pyridyl-methyl]-amino)-5-nitro-pyrimidine

[1962] HPLC/MS (method B): RT=2.26 min.; [M+H]+=371,1

[1963] (611)2-(4-chlorophenylamino)-4-(1-ethyl-3-piperidinylamino)-5-nitro-pyrimidine

[1964] HPLC/MS (method B): RT=2.34 min.; [M+H]+=377,2

[1965] (612)2-(4-chlorophenylamino)-4-(2-dimethylamino-cyclohexylamino)-5-nitro-pyrimidine

[1966] HPLC/MS (method B): RT=2.53 min.; [M+H]+=391,2

[1967] (613)2-(4-chlorophenylamino)-4-(4-(3-hydroxy-1-propyl)-1-piperidinyl)-5-nitro-pyrimidine

[1968] HPLC/MS (method B): RT=3.16 min.; [M+H]+=392,2

[1969] (614)2-(4-chlorophenylamino)-4-(4-(3-hydroxy-1-propyl)-1-piperazinyl)-5-nitro-pyrimidine

[1970] HPLC/MS (method B): RT=2.19 min.; [M+H]+=393,2

[1971] (615)2-(4-chlorophenylamino)-4-(N-methyl-N-[3-(4-pyridyl)-1-propyl]-amino)-5-nitro-pyrimidine

[1972] HPLC/MS (method B): RT=2.39 min.; [M+H]+=399,2

[1973] (616)2-(4-chlorophenylamino)-4-(4-dimethylamino-2-phenyl-1-butylamino)-5-nitro-pyrimidine

[1974] HPLC/MS (method B): RT=2.6 min.; [M+H]+=441,2

[1975] (617)2-(4-chlorophenylamino)-4-(2-(3-diethylamino-1-propyl)-1-piperidinyl)-5-nitro-pyrimidine

[1976] HPLC/MS (method B): RT=2.77 min.; [M+H]+=447,3

[1977] (618)2-(4-chlorophenylamino)-4-(bis-[3-pyridylmethyl]-amino)-5-nitro-pyrimidine

[1978] HPLC/MS (method B): RT=1.85 min.; [M+H]+=448,2

[1979] (619)2-(4-chlorophenylamino)-4-(4-(N-methyl-N-[2-methoxycarbonyl-1-ethyl]-amino)-1-piperidinyl)-5-nitro-pyrimidine

[1980] HPLC/MS (method B): RT=2.11 min.; [M+H]+=449,3

[1981] (620)2-(4-chlorophenylamino)-4-(2-(4-(2H-pyridazin-3-on-6-yl)-phenyl)-1-ethylamino)-1-piperidinyl)-5-nitro-pyrimidine

[1982] (621)2-(4-chlorophenylamino)-4-(3-(4-amino-3,5-dichlorophenyl)-1-propylamino)-5-nitro-pyrimidine

[1983] (622)2-(4-chlorophenylamino)-4-(4-(2-(N-[dimethylaminocarbonylmethyl]-N-methyl-amino)-1-ethyl-amino)-1-piperidinyl)-5-nitro-pyrimidine

[1984] HPLC/MS (method B): RT=2.21 min.; [M+H]+=476,34

[1985] (623)2-(4-chlorophenylamino)-4-(2-(2-(2-diethylamino-1-ethoxy)-1-ethyl)-1-piperidinyl)-5-nitro-pyrimidine

[1986] (624) 2-(4-chlorophenylamino)-4-(4-(2-(2-diethylamino-1-ethoxy)-1-ethyl)-1-piperidinyl)-5-nitro-pyrimidine

[1987] (625)2-(4-chlorophenylamino)-4-(5-(3-carboxy-1-propyl)-indan-2-yl-amino)-5-nitro-pyrimidine

[1988] (626)2-(4-chlorophenylamino)-4-(2-ethoxycarbonyl-1-(3-pyridyl)-1-ethyl-amino)-5-nitro-pyrimidine

[1989] HPLC/MS (method B): RT=2.43 min.; [M+H]+=443,2

[1990] (627)2-(4-chlorophenylamino)-4-(1,1-dimethyl-3-(2-oxo-3-pyridin-4-yl-imidazolidin-1-yl)-propylamino)-5-nitro-pyrimidine

[1991] HPLC/MS (method B): RT=2.4 min.; [M+H]+=497,0

[1992] (628)2-(2-bromo-benzylamino)-4-(S-oxido-thiomorpholino)-5-nitro-pyrimidinePrepared from 2-chloro-4-thiocyanato-5-nitro-pyrimidine,2-bromobenzylamine and Hünig base in dioxane, evaporating the reactionmixture and further reacting with thiomorpholine-S-oxide and Hünig basein DMF. (The intermediate product was not isolated.)

[1993] Melting point: 246-250° C.

[1994] Rf=0.41 (silica gel; cyclohexane:ethyl acetate:methanol=10:8:2)

[1995] (629) 2-(4-chlorophenylamino)-4-morpholino-5-nitro-pyrimidine

[1996] melting point: 218-220° C.

[1997] (630)2-(4-chlorophenylamino)-4-(2-cyanethylamino)-5-nitro-pyrimidine meltingpoint: 203° C.

[1998] (631)2-(4-chlorophenylamino)-4-(ethoxycarbonylmethylamino)-5-nitro-pyrimidine

[1999] melting point: 202-204° C.

[2000] (632)2-(4-chlorophenylamino)-4-[2-(ethoxycarbonyl)ethylamino]-5-nitro-pyrimidine

[2001] melting point: 163-165° C.

[2002] (633)2-(3,4-dichlorophenylamino)-4-[3-(dimethylamino)propylamino]-5-nitro-pyrimidine

[2003] melting point: 168-170° C.

[2004] (634)2-(3,4-dichlorophenylamino)-4-(2-hydroxyethylamino)-5-nitro-pyrimidine

[2005] melting point: 196° C.

[2006] (635)2-(3,4-dichlorophenylamino)-4-(2-methoxyethylamino)-5-nitro-pyrimidine

[2007] melting point: 165° C.

[2008] (636)2-(3,4-dichlorophenylamino)-4-[2-(dimethylamino)ethylamino]-5-nitro-pyrimidine

[2009] melting point: 175-176° C.

[2010] (637)2-(3,4-dichlorophenylamino)-4-(2-morpholinoethylamino)-5-nitro-pyrimidine

[2011] melting point: 190° C.

[2012] (638)2-(3,4-dichlorophenylamino)-4-[4-(dimethylamino)butylamino]-5-nitro-pyrimidine

[2013] melting point: 110° C.

[2014] (639)2-(3,4-dichlorophenylamino)-4-[(2-ethoxycarbonyl-ethyl)amino]-5-nitro-pyrimidine

[2015] melting point: 137° C.

[2016] (640)2-(4-chlorophenylamino)-4-[2-(methansulphonylamino)ethylamino]-5-nitro-pyrimidine

[2017] Prepared from compound 140 of Example 1 by subsequent reactionwith methanesulphonylchloride/triethylamine.

[2018] melting point: 231-235° C.

[2019] (641)2-(4-chlorophenylamino)-4-(carboxymethylamino)-5-nitro-pyrimidine

[2020] Prepared from compound 631 of Example 1 by subsequent reactionwith 1N sodium hydroxide solution in tetrahydrofuran.

[2021] melting point: >300° C.

[2022] Rf value: 0,36 (silica gel; methylene chloride/methanol=9:1)

[2023] (642)2-(3,4-dichlorophenylamino)-4-[(2-carboxyethyl)amino]-5-nitro-pyrimidine

[2024] Prepared from compound 639 of Example 1 by subsequent reactionwith 1N sodium hydroxide solution in tetrahydrofuran.

[2025] Rf value: 0,16 (silica gel; cyclohexane/ethylacetate/methanol=7:2:1)

[2026] (643)2-(3-bromophenylamino)-4-[1-hydroxy-3-methyl-2-butylamino]-5-trifluoromethyl-pyrimidinePrepared from compound 5 of Example 3.

[2027] (644)2-[4-(1,2,4,5-tetrahydro-benzo[d]azepin-3-yl-methyl)-phenylamino]-4-morpholino-255-trifluoromethyl-pyrimidine

[2028] melting point: 172° C.

[2029] (645)2-[4-(1,2,4,5-tetrahydro-benzo[d]azepin-3-yl-methyl)-phenylamino]-4-(4-methyl-1-piperazinyl)-5-trifluoromethyl-pyrimidine

[2030] melting point: 217° C. (decomposition)

[2031] (646)2-[4-(1,2,4,5-tetrahydro-benzo[d]azepin-3-yl-methyl)-phenylamino]-4-(1,4,6,7-tetrahydro-imidazo[4,5-c]pyridin-5-yl)-5-trifluoromethyl-pyrimidine

[2032] melting point: 350° C. (decomposition)

[2033] (647)2-[4-(1,2,4,5-tetrahydro-benzo[d]azepin-3-yl-methyl)-phenylamino]-4-[(2-carboxyethyl)amino]-5-trifluoromethyl-pyrimidine

[2034] melting point: 120° C. (decomposition)

[2035] Prepared using beta-alanine in sodium hydroxide solution.

[2036] (648)2-[4-(1,2,4,5-tetrahydro-benzo[d]azepin-3-yl-methyl)-phenylamino]-4-(trans-4-dimethylamino-cyclohexylamino)-5-trifluoromethyl-pyrimidine-dihydrochloride

[2037] melting point: 293° C. (decomposition)

[2038] (649)2-[4-(1,2,4,5-tetrahydro-benzo[d]azepin-3-yl-methyl)-phenylamino]-4-(2-acetylamino-ethylamino)-5-trifluoromethyl-pyrimidine-dihydrochlorideBIBX2827BS,LD3YED00783B.

[2039] melting point: 205° C. (decomposition)

[2040] (650)4-[4-(2-Methylamino-ethylamino)-5-trifluoromethyl-pyrimidin-2-ylamino]-benzamide

[2041] Prepared analogously to 1(80).

[2042] melting point: 187-190° C.

[2043] R_(f)=0,08 (silica gel; methylene chloride:methanol=4:1)

[2044] HPLC/MS (method G): RT=2.45 min.; [M+H]+=355; Abs. λ max=277,9 nm

[2045] (651)N-{2-[2-(3-dimethylsulphamoyl-phenylamino)-5-trifluoromethyl-pyrimidin-4-ylamino]-ethyl}-acetamide

[2046] Melting point: 202-203° C.

[2047] Rf value: 0.57 (silica gel; methylene chloride/methanol=9:1)

[2048] HPLC/MS (method D): RT=5,33 min.; [M+H]+=447; Abs./max 235 nm

[2049] (652)N-{2-[5-Bromo-2-(4-dimethylsulphamoyl-phenylamino)-pyrimidin-4-ylamino]-ethyl}-acetamide

[2050] Melting point: 226

[2051] Rf value: 0,42 (silica gel; methylene chloride/methanol=9:1)

[2052] HPLC/MS (method D): RT=4,84 min.; [M+H]+=459; Abs./max 273 nm

[2053] (653)N-(2-{2-[3-(morpholine-4-sulphonyl)-phenylamino]-5-trifluoromethyl-pyrimidin-4-ylamino}-ethyl)-acetamide

[2054] Melting point: 214° C.

[2055] Rf value: 0.51 (silica gel; methylene chloride/methanol=9:1)

[2056] HPLC/MS (method D): RT=5,31 min.; [M+H]+=489; Abs./max 235 nm

[2057] (654)N-{2-[2-(1-methyl-1H-indazol-6-ylamino)-5-trifluoromethyl-pyrimidin-4-ylamino]-ethyl}-acetamide

[2058] Melting point: 260-261° C.

[2059] Rf value: 0.39 (silica gel; methylene chloride/methanol=9:1)

[2060] HPLC/MS (method D): RT=4,78 min.; [M+H]+=394; Abs./max 250 nm

[2061] (655)N-{2-[2-(1-methyl-1H-indazol-5-ylamino)-5-trifluoromethyl-pyrimidin-4-ylamino]-ethyl}-acetamide

[2062] Melting point: 265-266° C.

[2063] Rf value: 0.25 (silica gel; methylene chloride/methanol=9:1)

[2064] HPLC/MS (method D): RT=4,47 min.; [M+H]+=394; Abs./max 254 nm

[2065] (656)N-{2-[2-(2-methyl-2H-indazol-6-ylamino)-5-trifluoromethyl-pyrimidin-4-ylamino]-ethyl}-acetamide

[2066] Melting point: 254-255° C.

[2067] Rf value: 0.45 (silica gel; methylene chloride/methanol=9:1)

[2068] HPLC/MS (method D): RT=4,45 min.; [M−H]−=394; Abs./max 250 nm

[2069] (657){2-[5-Bromo-2-(3-dimethylsulphamoyl-phenylamino)-pyrimidin-4-ylamino]-ethyl}-acetamide

[2070] Melting point: 192° C.

[2071] Rf value: 0.43 (silica gel; methylene chloride/methanol=9:1)

[2072] HPLC/MS (method D): RT=4,75 min.; [M+H]+=459; Abs. λ max=268 nm

[2073] (658)N-(2-{5-Bromo-2-[3-(morpholine-4-sulphonyl)-phenylamino]-pyrimidin-4-ylamino}-ethyl)-acetamide

[2074] Melting point: 212° C.

[2075] Rf value: 0.47 (silica gel; methylene chloride/methanol=9:1)

[2076] HPLC/MS (method D): RT=4,76 min.; [M+H]+=501; Abs. λ max=268 nm

[2077] (659)N-(2-{2-[4-(2-dimethylamino-ethyl)-phenylamino]-5-trifluoromethyl-pyrimidin-4-ylamino}-ethyl)-acetamide

[2078] Melting point: 110° C.

[2079] R_(f)=0.13 (silica gel; methylene chloride:methanol=1:2)

[2080] HPLC/MS (method D): RT=1,96 min.; [M+H]+=411; Abs. λ max=256

[2081] (660)N-{2-[2-(4-piperidin-1-ylmethyl-phenylamino)-5-trifluoromethyl-pyrimidin-4-ylamino]-ethyl}-acetamide

[2082] Melting point: 223-226° C.

[2083] R_(f)=0.23 (silica gel; methylene chloride:methanol=1:1)

[2084] HPLC/MS (method D): RT=3,94 min.; [M+H]+=437; Abs. λ max=265 nm

[2085](661)1-{3-[5-Bromo-2-(3,4-dichloro-phenylamino)-pyrimidin-4-ylamino]-propyl}-pyrrolidin-2-one

[2086] Melting point: 234° C.

[2087] R_(f)=0.56 (silica gel; methylene chloride:methanol=9:1)

[2088] HPLC/MS (method C): RT=4,30 min.; [M+H]+=460; Abs. λ max=274 nm

[2089] (662)1-{3-[5-Bromo-2-(3,4-dichloro-phenylamino)-pyrimidin-4-ylamino]-propyl}-pyrrolidin-2-one

[2090] Melting point: 216-218° C.

[2091] R_(f)=0.55 (methylene chloride:methanol=5:1)

[2092] HPLC/MS (method C): RT=3,11 min.; [M+H]+=435; Abd. λ max=278

[2093] (663)4-[4-(2-acetylamino-ethylamino)-5-bromo-pyrimidin-2-ylamino]-benzamide

[2094] Melting point: 265-266° C.

[2095] R_(f)=0.22 (silica gel; methylene chloride:methanol=9:1)

[2096] HPLC/MS (method D): RT=3,93 min.; [M+H]+=395; Abs. λ max=278

[2097] (664)N-(2-{2-[3-(benzyl-methyl-sulphamoyl)-phenylamino]-5-trifluoromethyl-pyrimidin-4-ylamino}-ethyl)-acetamide

[2098] Melting point: 126° C.

[2099] R_(f)=0.61 (silica gel; methylene chloride:methanol=9:1)

[2100] HPLC/MS (method D): RT=6.33 min.; [M+H]+=523; Abs. λ max=238 nm

[2101] (665)N-(2-{2-[3-(4-methyl-piperazin-1-sulphonyl)-phenylamino]-5-trifluoromethyl-pyrimidin-4-ylamino}-ethyl)-acetamide

[2102] Melting point: 247° C.

[2103] R_(f)=0.44 (silica gel; methylene chloride:methanol=9:1)

[2104] HPLC/MS (method D): RT=4.36 min.; [M+H]+=502; Abs. λ max=234 nm

[2105] (666)4-{4-[(3-aminomethyl-cyclohexylmethyl)-amino]-5-trifluoromethyl-pyrimidin-2-ylamino}-benzamide

[2106] Melting point: 209-212° C.

[2107] R_(f)=0,03 (silica gel; methylene chloride:methanol=4:1)

[2108] HPLC/MS (method G): RT=2.87 min.; [M+H]+=423; Abs. λ max=279,8 nm

[2109] (667)N-{2-[2-(4-Morpholin-4-ylmethyl-phenylamino)-5-trifluoromethyl-pyrimidin-4-ylamino]-ethyl}-acetamide

[2110] Melting point: 70° C.

[2111] R_(f)=0.69 (silica gel; methylene chloride:methanol=9:1)

[2112] HPLC/MS (method D): RT=3.98 min.; [M+H]+=439; Abs. λ max 266 nm

[2113] (668)N-{2-[2-(4-cyano-3-trifluoromethyl-phenylamino)-5-trifluoromethyl-pyrimidin-4-ylamino]-ethyl}-acetamide

[2114] Melting point: 237° C.

[2115] R_(f)=0.50 (silica gel; methylene chloride:methanol=9:1)

[2116] HPLC/MS (method D): RT=6,35 min.; [M+H]+=433; Abs. λ max=318 nm

[2117] (669)N-{2-[2-(3-Chloro-4-cyano-phenylamino)-5-trifluoromethyl-pyrimidin-4-ylamino]-ethyl}-acetamide

[2118] Melting point: 250° C.

[2119] R_(f)=0.45 (silica gel; methylene chloride:methanol=9:1)

[2120] HPLC/MS (method D): RT=6,20 min.; [M+H]+=399; Abs. λ max=309 nm

[2121] (670)1-(2-{[2-(3,4-dichloro-phenylamino)-5-trifluoromethyl-pyrimidin-4-yl]-methyl-amino}-ethyl)-pyrrolidin-2-one

[2122] Melting point: 164° C.

[2123] R_(f)=0.11 (silica gel; hexane:ethyl acetate=1:1)

[2124] HPLC/MS (method D): RT=6,862 min.; [M+H]+=450; Abs. λ max=270 nm

[2125](671)1-{2-[2-(3,4-dichloro-phenylamino)-5-trifluoromethyl-pyrimidin-4-ylamino]-ethyl}-pyrrolidin-2-one

[2126] Melting point: 218° C.

[2127] R_(f)=0.23 (silica gel; hexane:ethyl acetate=1:1)

[2128] HPLC/MS (method D): RT=6,496 min.; [M+H]+=436; Abs. λ max=274 nm

[2129] (672)4-[4-(4-methanesulphonylamino-piperidin-1-yl)-5-trifluoromethyl-pyrimidin-2-ylamino]-N,N-dimethyl-phenylsulphonamide

[2130] Melting point: 218° C.

[2131] R_(f)=0.46 (silica gel; hexane:ethyl acetate=33:67)

[2132] HPLC/MS (method D): RT=6,353 min.; [M+H]+=523; Abs. λ max 294 nm

[2133] (673)4-{4-[4-(methanesulphonyl-methyl-amino)-piperidin-1-yl]-5-trifluoromethyl-pyrimidin-2-ylamino}-N,N-dimethyl-phenylsulphonamide

[2134] Melting point: 226° C.

[2135] R_(f)=0.27 (silica gel; hexane:ethyl acetate=1:1)

[2136] HPLC/MS (method D): RT=6,652 min.; [M+H]+=537; Abs. λ max=294 nm

[2137] (674)3-[2-(1-methyl-1H-indazol-6-ylamino)-5-trifluoromethyl-pyrimidin-4-ylamino]-propylamine

[2138] 4.7 g of N-Z-1,3-diaminopropane hydrochloride, 10 ml of Hünigbase and 5.2 g of2-(1-methyl-1H-indazol-6-ylamino)-4-chloro-5-trifluoromethyl-pyrimidincare suspended in 160 ml of dioxane and DMF is added until all thecomponents have dissolved. After 17 hours at 80° C. the mixture is takenup in ethyl acetate, extracted with H₂O, the organic phase is then driedand concentrated by rotary evaporation. The product is chromatographedwith toluene: ethyl acetate (1:1) over silica gel. The intermediateproduct is dissolved in ethanol, methanol and toluene (4:1:3, 800 ml), 1g of Pd(OH)₂ is added and the mixture is hydrogenated at 50 psi and 40°C. over 28 hours. After the catalyst has been filtered off and thesolution concentrated, the product remains.

[2139] Melting point: 201° C., Subl.

[2140] R_(f)=0.15 (silica gel; methylene chloride:methanol=95:5)

[2141] HPLC/MS (method B): RT=4,35 min.; [M+H]+=366; Abs. λ max=226 nm

[2142] (675)N-{1-[2-(3,4-dichloro-phenylamino)-5-trifluoromethyl-pyrimidin-4-yl]-piperidin-4-yl}-methanesulphonamide

[2143] Melting point: 200° C.

[2144] R_(f)=0.42 (silica gel; hexane:ethyl acetate=1:1)

[2145] HPLC/MS (method D): RT=7.105 min.; [M+H]+=486; Abs. λ max=274 nm

[2146] (676)(4-Chloro-phenyl)-[4-(1-oxo-1,4-thiomorpholin-4-yl)-5-trifluoromethyl-pyrimidin-2-yl]-amine

[2147] Melting point: 213-216° C.

[2148] R_(f)=0.42 (silica gel; hexane:ethyl acetate=2:1)

[2149] HPLC/MS (method D): RT=6.015 min.; [M+H]+=391; Abs. λ max=259 nm

[2150] (677)(3-Chloro-phenyl)-[4-(4-pyridin-2-yl-piperazin-1-yl)-5-trifluoromethyl-pyrimidin-2-yl]-amine

[2151] Melting point: 146-147° C.

[2152] R_(f)=0.66 (silica gel; methylene chloride:methanol=95:5)

[2153] HPLC/MS (method D): RT=5.203 min.; [M+H]+=435; Abs. λ max=271 nm

[2154] (678)1-{3-[2-(3,5-dichloro-phenylamino)-5-trifluoromethyl-pyrimidin-4-ylamino]-propyl}-pyrrolidin-2-one

[2155] Melting point: 174-175° C.

[2156] R_(f)=0.10 (silica gel; hexane:ethyl acetate=1:1)

[2157] HPLC/MS (method D): RT=6.309 min.; [M+H]+=450; Abs. λ max=230 nm

[2158] (679)(3-Chloro-phenyl)-[4-(1-oxo-1-thiomorpholin-4-yl)-5-trifluoromethyl-pyrimidin-2-yl]-amine

[2159] Melting point: 214-217° C.

[2160] R_(f)=0.51 (silica gel; methylene chloride:methanol=95:5)

[2161] HPLC/MS (method D): RT=5,571 min.; [M+H]+=391; Abs. λ max=270 nm

[2162] (680)(4-Chloro-phenyl)-[4-(4-pyridin-2-yl-piperazin-1-yl)-5-trifluoromethyl-pyrimidin-2-yl]-amine

[2163] Melting point: 164-166° C.

[2164] R_(f)=0.43 (silica gel; hexane:ethyl acetate:methanol=5:4:1)

[2165] (681) methyl{1-[2-(4-chloro-phenylamino)-5-trifluoromethyl-pyrimidin-4-yl]-piperidin-4-yl}-acetate

[2166] R_(f)=0.86 (silica gel; hexane:ethyl acetate=1:1)

[2167] HPLC/MS (method D): RT=7,521 min.; [M+H]+=429; Abs. λ max=266 nm

[2168] (682){1-[2-(4-Chloro-phenylamino)-5-trifluoromethyl-pyrimidin-4-yl]-piperidin-4-yl}-5acetic acid

[2169] Melting point: 200-201° C.

[2170] R_(f)=0.44 (silica gel; hexane:ethyl acetate=1:1)

[2171] HPLC/MS (method D): RT=6,623 min.; [M+H]+=415; Abs. λ max=270 nm

[2172] (683)N,N-dimethyl-4-{4-[2-(2-oxo-pyrrolidin-1-yl)-ethylamino]-5-trifluoromethyl-pyrimidin-2-ylamino}-phenylsulphonamide

[2173] Melting point: 258-261° C.

[2174] R_(f)=0.14 (silica gel; hexane:ethyl acetate=1:2)

[2175] HPLC/MS (method D): RT=5,828 min.; [M+H]+=473; Abs. λ max=302 nm

[2176] (684)N,N-dimethyl-4-(4-{methyl-[2-(2-oxo-pyrrolidin-1-yl)-ethyl]-amino}-5-trifluoromethyl-pyrimidin-2-ylamino)-benzenesulphonamide

[2177] Melting point: 147-150° C.

[2178] R_(f)=0.13 (silica gel; hexane:ethyl acetate=2:1)

[2179] HPLC/MS (method D): RT=6,15 min.; [M+H]+=487; Abs. λ max=290 nm

[2180] (685)N-(1,1-dimethyl-2-{2-[4-(morpholine-4-sulphonyl)-phenylamino]-5-trifluoromethyl-pyrimidin-4-ylamino}-ethyl)-acetamide

[2181] Melting point: 105-107° C.

[2182] R_(f)=0.39 (silica gel; ethyl acetate)

[2183] HPLC/MS (method D): RT=5,89 min.; [M+H]+=517; Abs. λ max=302 nm

[2184] (686)N4-methyl-N-4-(2-methylamino-ethyl)-N-2-[4-(morpholine-4-sulphonyl)-phenyl]-5-trifluoromethyl-pyrimidine-2,4-diamineformate

[2185] Melting point: 184-186° C.

[2186] R_(f)=0.09 (silica gel; methylene chloride:methanol=9:1)

[2187] HPLC/MS (method D): RT=4.83 min.; [M+H]+=475; Abs. λ max=302 nm

[2188] (687)N,N-dimethyl-4-{4-[methyl-(2-methylamino-ethyl)-amino]-5-trifluoromethyl-pyrimidin-2-ylamino}-benzenesulphonamidehydrochloride

[2189] Melting point: 235-238° C.

[2190] R_(f)=0.10 (silica gel; methylene chloride:methanol=9:1)

[2191] HPLC/MS (method D): RT=4.86 min.; [M+H]+=433; Abs. λ max=298 nm

[2192] (688) benzyl(2-{2-[4-(morpholin-4-sulphonyl)-phenylamino]-5-trifluoromethyl-pyrimidin-4-ylamino}-ethyl)-carbonate

[2193] Melting point: 166-169° C.

[2194] R_(f)=0.61 (silica gel; ethyl acetate)

[2195] HPLC/MS (method D): RT=6.64 min.; [M+H]+=581; Abs. λ max=306 nm

[2196] (689)N4-(2-amino-ethyl)-N-2-[4-(morpholine-4-sulphonyl)-phenyl]-5-trifluoromethyl-pyrimidine-2,4-diamine

[2197] Melting point: 169-170° C.

[2198] R_(f)=0.20 (silica gel; methylene chloride:methanol=1:1)

[2199] HPLC/MS (method D): RT=4.88 min.; [M+H]+=447; Abs. λ max=302 nm

[2200] (690)N-(2-{[2-(4-dimethylsulphamoyl-phenylamino)-5-trifluoromethyl-pyrimidin-4-yl]-methyl-amino}-ethyl)-N-methyl-acetamide

[2201] Melting point: 156-158° C.

[2202] R_(f)=0.17 (silica gel; ethyl acetate)

[2203] HPLC/MS (method D): RT=6.12 min.; [M+H]+=475; Abs. λ max=282 nm

[2204] (691)N-methyl-N-[2-(methyl-{2-[4-(morpholine-4-sulphonyl)-phenylamino]-5-trifluoromethyl-pyrimidin-4-yl}-amino)-ethyl]-acetamide

[2205] Melting point: 158-161° C.

[2206] R_(f)=0.15 (silica gel; ethyl acetate)

[2207] HPLC/MS (method D): RT=6.04 min.; [M+H]+=517; Abs. λ max=294 nm

[2208] (692)N-(2-{2-[4-(propane-2-sulphonyl)-phenylamino]-5-trifluoromethyl-pyrimidin-4-ylamino}-ethyl)-acetamide

[2209] Melting point: 198-200° C.

[2210] R_(f)=0.60 (silica gel; methylene chloride:methanol=9:1)

[2211] HPLC/MS (method C): RT=3,97 min.; [M+H]+=446; Abs. λ max=302 nm

[2212] (693)4-[4-(3-aminopropylamino)-5-trifluoromethyl-pyrimidin-2-ylamino]-benzamide

[2213] The compound was obtained analogously to Example 1(674)

[2214] (694)N,N-dimethyl-4-[4-(3,4,6,7-tetrahydro-imidazo[4,5-c]pyridin-5-yl)-5-trifluoromethyl-pyrimidin-2-ylamino]-phenylsulphonamide

[2215] Melting point: 230° C. decomposition

[2216] R_(f)=0.28 (silica gel; methylene chloride:methanol=95:5)

[2217] HPLC/MS (method D): RT=5.20 min.; [M+H]+=468; Abs. λ max=286, 302nm

[2218] (695)[4-(Morpholin-4-sulphonyl)-phenyl]-[4-(3,4,6,7-tetrahydro-imidazo[4,5-5]pyridin-5-yl)-5-trifluoromethyl-pyrimidin-2-yl]-amine

[2219] Melting point: >270° C. decomposition

[2220] R_(f)=0.33 (silica gel; methylene chloride:methanol=95:5)

[2221] HPLC/MS (method D): RT=5,30 min.; [M+H]+=510; Abs. λ max=302 nm

[2222] (696) benzyl{3-[2-(1-methyl-1H-indazol-6-ylamino)-5-trifluoromethyl-pyrimidin-4-ylamino]-propyl}-carbaminate

[2223] Melting point: 139° C.

[2224] R_(f)=0,30 (silica gel; toluene: ethyl acetate=1:1)

[2225] HPLC/MS (method D): RT=6,37 min.; [M+H]+=500; Abs. λ max=250 nm

EXAMPLE 2

[2226]2-(4-carboxyphenylamino)-4-(2-acetylamino-ethylamino)-5-nitro-pyrimidine-hydrochloride

[2227] 100 mg of 4-aminobenzoic acid in 5 ml ethanol are added to 173 mgof 2-chloro-4-(2-acetylamino-ethylamino)-5-nitro-pyrimidine (compound(1) of Example II) in 5 ml ethanol at ambient temperature. Two drops ofconcentrated hydrochloric acid are added and the mixture is stirred for12 h. Then 50 ml of water are added. The precipitate is suction filteredand dried in the air. The residue is stirred with 30 ml methylenechloride, suction filtered and dried.

[2228] Yield: 135 mg (51% of theory), Melting point: 290° C.(decomposition)

[2229] R_(f)=0.2 (silica gel; methylene chloride:methanol=9:1)

[2230] The following compounds are obtained analogously to Example 2:

[2231] (1)2-(3,4-dichlorophenylamino)-4-(2-acetylamino-ethylamino)-5-trifluoromethylsulphanyl-pyrimidine-hydrochloride

[2232] Melting point: 196° C.

[2233] R_(f)=0.5 (silica gel; methylene chloride:methanol:conc.ammonia=16:3:1)

[2234] Prepared from compound (3) of Example II.

[2235] (2)2-(3,4-dichlorophenylamino)-4-(2-acetylamino-ethylamino)-5-bromo-pyrimidine-hydrochloride

[2236] Melting point: 260° C. (decomposition)

[2237] Prepared from compound (4) of Example II.

[2238] (3)2-(3,4-dichlorophenylamino)-4-(2-acetylamino-ethylamino)-5-trifluoromethyl-pyrimidine-hydrochloride

[2239] Melting point: 227° C.

[2240] Prepared from the compound of Example II.

[2241] (4)N-{2-[2-(4-amino-phenylamino)-5-trifluoromethyl-pyrimidin-4-ylamino]-ethyl}-acetamide

[2242] 6.9 g of p-phenylenediamine are added to 3 g ofN-[2-(2-chloro-5-trifluoromethyl-pyrimidin-4-ylamino)-ethyl]-acetamidein 25 ml glacial acetic acid and the mixture is stirred for 2 hours atambient temperature. After removal of the acetic acid under reducedpressure the crude product is taken up in methylene chloride andextracted with 2 M sodium carbonate solution. The aqueous phase iswashed with methylene chloride, the organic phases are combined anddried over sodium sulphate. After evaporation, the material ischromatographed over silica gel with methylene chloride/isopropanol(20:1).

[2243] Yield: 3 g

[2244] Melting point: 175° C. decomposition

[2245] R_(f)=0.35 (silica gel; methylene chloride: isopropanol=8:2)

[2246] APCI-MS [M+H]+=355

[2247] 1H-NMR(D₆-DMSO, 300 MHz) δ: 1.80 (s, 3H), 3.25 (m, 2H), 3.47 (m,2H), 4.78 (bs, 2H), 6.50 (d, 2H), 6.93 (bs, 2H), 7.29 (d, 2H), 7.90 (t,1H), 8.08 (s, 1H), 9.13 (s, 1H).

[2248] (5)2-(3,4-dichlorophenylamino)-4-(2-acetylamino-ethylamino)-5-methylsulphanyl-pyrimidine-hydrochloride

[2249] Melting point: 220° C.

[2250] Prepared from compound (2) of Example II.

[2251] (6)2-(1-naphthylamino)-4-[N-(trans-4-hydroxy-cyclohexyl)-N-methyl-amino]-5-nitro-pyrimidine

[2252] HPLC/MS (Method B): RT=2,55 min.; [M+H]+=394,2

[2253] (7)2-(4-bromophenylamino)-4-(2-acetylamino-ethylamino)-5-trifluoromethyl-pyrimidine

[2254] HPLC/MS (Method A): RT=5.83 min.; [M+H]+=420.1

[2255] (8)2-(4-aminosulphonyl-phenylamino)-4-(2-acetylamino-ethylamino)-5-trifluoromethyl-pyrimidine

[2256] HPLC/MS (Method A): RT=4.95 min.; [M+H]+=419.1

[2257] (9)2-(3-chloro-phenylamino)-4-(2-acetylamino-ethylamino)-5-trifluoromethyl-pyrimidine

[2258] HPLC/MS (Method A): RT=5.84 min.; [M+H]+=374.1

[2259] (10)2-(3-Nitro-phenylamino)-4-(2-acetylamino-ethylamino)-5-trifluoromethyl-pyrimidine

[2260] Melting point: 201-204° C.

[2261] R_(f)=0.60 (silica gel; methylene chloride:methanol=95:5)

[2262] HPLC/MS (method D): RT=5.398 min.; [M+H]+=385; Abs. λ max=266 nm

[2263] (11)2-(4-(N-Methyl-N-methylsulphonyl)amino-phenylamino)-4-(2-acetylamino-ethylamino)-5-trifluoromethyl-pyrimidine

[2264] HPLC/MS (method A): RT=5.15 min.; [M+H]+=447.2

[2265] (12)2-(3-bromo-phenylamino)-4-(2-acetylamino-ethylamino)-5-trifluoromethyl-pyrimidine

[2266] R_(f)=0.60 (silica gel; cyclohexane:ethyl acetate=1:2)

[2267] HPLC/MS (method D): RT=5.68 min.; [M+H]+=419; Abs. λ max=254 nm

[2268] (13)2-(4-chloro-3-trifluoromethyl-phenylamino)-4-(2-acetylamino-ethylamino)-5-trifluoromethyl-pyrimidine

[2269] HPLC/MS (method A): RT=6.71 min.; [M+H]+=442.1

[2270] (14)2-(4-bromo-3-chloro-phenylamino)-4-(2-acetylamino-ethylamino)-5-trifluoromethyl-pyrimidine

[2271] HPLC/MS (method A): RT=6.57 min.; [M+H]+=454.0

[2272] (15)2-(3,5-Dichloro-phenylamino)-4-(2-acetylamino-ethylamino)-5-trifluoromethyl-pyrimidine

[2273] HPLC/MS (method A): RT=6.73 min.; [M+H]+=408.1

[2274] (16)2-(4-chloro-phenylamino)-4-(2-acetylamino-ethylamino)-5-trifluoromethyl-pyrimidine

[2275] HPLC/MS (method A): RT=5.71 min.; [M+H]+=374.1

[2276] (17)2-(4-Morpholino-phenylamino)-4-(2-acetylamino-ethylamino)-5-nitro-pyrimidin

[2277] HPLC/MS (method A): RT=5.22 min.; [M+H]+=402.2

[2278] (18)2-(4-(N-Methyl-N-methylsulphonyl)amino-phenylamino)-4-(N-(trans-4-hydroxy-cyclohexyl)-N-methyl-amino)-5-nitro-pyrimidine

[2279] HPLC/MS (method A): RT=5.89 min.; [M+H]+=451.2

[2280] (19)2-(4-Diethylaminomethyl-phenylamino)-4-(2-acetylamino-ethylamino)-5-nitro-pyrimidine

[2281] HPLC/MS (method A): RT=4.7 min.; [M+H]+=402.2

[2282] (20)2-(1,3-Dihydro-2-oxo-indol-6-ylamino)-4-[N-(trans-4-hydroxy-cyclohexyl)-N-methyl-amino]-5-nitro-pyrimidine

[2283] HPLC/MS (method A): RT=5.51 min.; [M+H]+=399.2

[2284] (21)2-(4-(N-Methyl-N-methylsulphonyl)amino-phenylamino)-4-(2-acetylamino-ethylamino)-5-nitro-pyrimidine

[2285] HPLC/MS (method A): RT=5.46 min.; [M+H]+=424.2

[2286] (22)2-(3-Hydroxy-4-methyl-phenylamino)-4-(trans-4-hydroxy-cyclohexylamino)-5-trifluoromethyl-pyrimidine

[2287] HPLC/MS (method B): RT=1.61 min.; [M+H]+=383,3

[2288] (23)2-(3-Hydroxy-4-methyl-phenylamino)-4-[N-(trans-4-hydroxy-cyclohexyl)-N-methyl-amino]-5-nitro-pyrimidine

[2289] HPLC/MS (method B): RT=2.2 min.; [M+H]+=374,2

[2290] (24)2-(6-Indazolylamino)-4-[N-(trans-4-hydroxy-cyclohexyl)-N-methyl-amino]-5-nitro-pyrimidine

[2291] HPLC/MS (method B): RT=2.26 min.; [M+H]+=384,2

[2292] (25)2-(1-Naphthylamino)-4-(trans-4-hydroxy-cyclohexylamino)-5-trifluoromethyl-pyrimidine

[2293] (26)2-(4-(3-Diethylamino-1-propyloxy)-phenylamino)-4-(2-pyridyl-methylamino)-5-nitro-pyrimidine

[2294] HPLC/MS (method B): RT=1.26 min.; [M+H]+=452,3

[2295] (27)2-(3-Hydroxy-4-methyl-phenylamino)-4-(2-acetylamino-1-ethylamino)-5-trifluoromethyl-pyrimidine

[2296] HPLC/MS (method B): RT=1.49 min.; [M+H]+=370,2

[2297] (28)2-(4-Benzylaminocarbonyl-phenylamino)-4-[N-(2-hydroxyethyl)-N-methyl-amino]-5-nitro-pyrimidine

[2298] HPLC/MS (method B): RT=2.47 min.; [M+H]+=423,2

[2299] (29)2-(3-Carboxy-phenylamino)-4-[N-(trans-4-hydroxy-cyclohexyl)-N-methyl-amino]-5-nitro-pyrimidine

[2300] HPLC/MS (method B): RT=2.21 min.; [M+H]+=388,2

[2301] (30)2-(5-Carboxy-2-naphthylamino)-4-(2-acetylamino-1-ethylamino)-5-nitro-pyrimidine

[2302] HPLC/MS (method B): RT=2.22 min.; [M+H]+=411,2

[2303] (31)2-(5-Carboxy-2-naphthylamino)-4-(2-pyridyl-methylamino)-5-nitro-pyrimidine

[2304] (32)2-(5-Carboxy-2-naphthylamino)-4-(ethoxycarbonyl-methylamino)-5-nitro-pyrimidine

[2305] HPLC/MS (method B): RT=2.71 min.; [M+H]+=412,2

[2306] (33)2-(4-Phenylaminocarbonyl-phenylamino)-4-[N-(2-hydroxyethyl)-N-methyl-amino]-5-nitro-pyrimidine

[2307] HPLC/MS (method B): RT=2.56 min.; [M+H]+=409,2

[2308] (34)2-(4-(4-Methyl-1-piperazinyl)-phenylamino)-4-[N-(trans-4-hydroxy-cyclohexyl)-N-methyl-amino]-5-nitro-pyrimidine

[2309] HPLC/MS (method B): RT=1.77 min.; [M+H]+=442,3

[2310] (35)2-(3,4-Dichlorphenylamino)-4-(2-acetylamino-ethylamino)-5-methyl-pyrimidine-hydrochlorid

[2311] Melting point: 254° C.

[2312](36)1-{3-[2-(1H-Benzotriazol-5-ylamino)-5-trifluoromethyl-pyrimidin-4-ylamino]-propyl}-pyrrolidin-2-one

[2313] R_(f)=0.16 (silica gel; methylene chloride:methanol=95:5)

[2314] Melting point: 118° C.

[2315](37)1-{3-[2-(1H-Benzimidazol-5-ylamino)-5-trifluoromethyl-pyrimidin-4-ylamino]-propyl}-pyrrolidin-2-one

[2316] Melting point: 110-113° C.

[2317] R_(f)=0.43 (silica gel; methylene chloride:methanol=95:5)

[2318] HPLC/MS (method D): RT=5.00 min.; [M+H]+=420; Abs. λ max=246 nm

[2319](38)1-{3-[2-(1H-Indazol-6-ylamino)-5-trifluoromethyl-pyrimidin-4-ylamino]-propyl}-pyrrolidin-2-one

[2320] R_(f)=0.18 (silica gel; methylene chloride:methanol=95:5)

[2321] Melting point: 210° C.

[2322] HPLC/MS (method D): RT=5.20 min.; [M+H]+=420; Abs. λ max=246 nm

[2323](39)1-{3-[2-(1H-Indazol-5-ylamino)-5-trifluoromethyl-2,3-dihydro-pyrimidin-4-ylamino]-propyl}-pyrrolidin-2-one

[2324] R_(f)=0.27 (silica gel; methylene chloride:methanol 95:5) Meltingpoint: 202° C.

[2325] HPLC/MS (method D): RT=4.50 min.; [M+H]+=420; Abs. λ max=237 nm

[2326] (40)N-{2-[5-chloroo-2-(1H-indazol-6-ylamino)-pyrimidin-4-ylamino]-ethyl}-acetamide

[2327] Melting point: >260° C. decomposition

[2328] R_(f)=0,29 (silica gel; methylene chloride:methanol=9:1)

[2329] HPLC/MS (method F): RT=3,04 min.; [M+H]+=346; Abs. λ max=284 nm

[2330] (41)N,N-Dimethyl-4-{4-[3-(2-oxo-pyrrolidin-1-yl)-propylamino]-5-trifluoromethyl-pyrimidin-2-ylamino}-phenylsulphonamide

[2331] R_(f)=0.43 (silica gel; methylene chloride:methanol=95:5)

[2332] Melting point: 190-193° C.

[2333] HPLC/MS [M−H]−=485

[2334] (42)N-{2-[2-(1H-Benzotriazol-5-ylamino)-5-trifluoromethyl-pyrimidin-4-ylamino]-ethyl}-acetamide

[2335] R_(f)=0.17 (silica gel; methylene chloride:methanol=95:5) Meltingpoint: >300° C., decomposition

[2336] (43)N-{2-[2-(1H-Benzimidazol-5-ylamino)-5-trifluoromethyl-pyrimidin-4-ylamino]-ethyl}-acetamide

[2337] R_(f)=0.33 (silica gel; methylene chloride:methanol=95:5)

[2338] Melting point: 208-210° C.

[2339] HPLC/MS (method D): RT=3.90 min.; [M+H]+=380; Abs. λ max=240 nm

[2340] (44)N-{2-[2-(1H-Indazol-6-ylamino)-5-trifluoromethyl-pyrimidin-4-ylamino]-ethyl}-acetamide

[2341] R_(f)=0.21 (silica gel; methylene chloride:methanol=95:5)

[2342] Melting point: >300° C.

[2343] HPLC/MS (method D): RT=4.80 min.; [M+H]+=380; Abs. λ max 244 nm

[2344] (45)N-{2-[2-(1H-Indazol-5-ylamino)-5-trifluoromethyl-pyrimidin-4-ylamino]-ethyl}-acetamide

[2345] R_(f)=0.17 (silica gel; methylene chloride:methanol=95:5)

[2346] Melting point: >300° C. decomposition

[2347] HPLC/MS (method D): RT=4.20 min.; [M+H]+=380; Abs. λ max=246 nm

[2348] (46)N-(2-{2-[4-(2H-Tetrazol-5-yl)-phenylamino]-5-trifluoromethyl-pyrimidin-4-ylamino}-ethyl)-acetamide

[2349] Melting point: >300° C. decomposition

[2350] R_(f)=0.86 (silica gel; methylene chloride:methanol=1:1)

[2351] HPLC/MS (method D): RT=5.00 min.; [M+H]+=408; Abs. λ max=290 mm

[2352] (47)N-{2-[2-(4-Dimethylsulphamoyl-phenylamino)-5-trifluoromethyl-pyrimidin-4-ylamino]-ethyl}-acetamide

[2353] Melting point: 204° C.

[2354] R_(f)=0,79 (silica gel; methylene chloride:methanol=95:5)

[2355] HPLC/MS (method D): RT=5.60 min.; [M+H]+=447; Abs. λ max=300 nm

[2356](48)1-{3-[5-chloroo-2-(1H-indazol-6-ylamino)-pyrimidin-4-ylamino]-propyl}-pyrrolidin-2-on

[2357] Melting point: 188-191° C.

[2358] R_(f)=0,41 (silica gel; methylene chloride:methanol=9:1)

[2359] HPLC/MS (method F): RT=3.23 min.; [M+H]+=386; Abs. λ max=249 nrm

[2360] (49)N,N-Dimethyl-4-{4-[2-(2-oxo-imidazolidin-1-yl)-ethylamino]-5-trifluoromethyl-pyrimidin-2-ylamino}-phenylsulphonamid

[2361] Melting point: 163-164° C.

[2362] R_(f)=0,13 (silica gel; methylene chloride:methanol=98:2)

[2363] HPLC/MS (method D): RT=6,82 min.; [M+H]+=474; Abs. λ max=306 nm

[2364] (50)2-chloroo-5-{4-[3-(2-oxo-pyrrolidin-1-yl)-propylamino]-5-trifluoromethyl-pyrimidin-2-ylamino}-benzoicacid

[2365] Melting point: 236-239° C.

[2366] R_(f)=0,1 (silica gel; methylene chloride:methanol=9:1)

[2367] HPLC/MS (method G): RT=3.35 min.; [M+H]+=458; Abs. λ max=267 nm

[2368] (51)1-(2-{2-[4-(Morpholin-4-sulphonyl)-phenylamino]-5-trifluoromethyl-pyrimidin-4-ylamino}-ethyl)-imidazolidin-2-one

[2369] Melting point: 164° C.

[2370] R_(f)=0.10 (silica gel; methylene chloride:methanol=98:2)

[2371] HPLC/MS (method D): RT=5.63 min.; [M+H]+=516; Abs. λ max=302 nm

[2372] (52)1-{3-[2-(4-Hydroxymethyl-phenylamino)-5-trifluoromethyl-pyrimidin-4-ylamino]-propyl}-pyrrolidin-2-one

[2373] Melting point: 153° C.

[2374] R_(f)=0.18 (silica gel; methylene chloride:methanol=9:1)

[2375] HPLC/MS (method D): RT=4,75 min.; [M+H]+=410; Abs. λ max=256 nm

[2376] (53)2-{4-[4-(2-Acetylamino-ethylamino)-5-trifluoromethyl-pyrimidin-2-ylamino]-phenyl}-N,N-dimethyl-acetamide

[2377] Melting point: 182-184° C.

[2378] R_(f)=0,09 (silica gel; hexane:ethyl acetate: methanol=5:4:1)

[2379] HPLC/MS (method D): RT=4,357 min.; [M+H]+=425; Abs. λ max=246 nm

[2380] (54)1-[2-(3,4-Dichloro-phenylamino)-5-trifluoromethyl-pyrimidine-4-yl]-azepan-4-one

[2381] Melting point: 147-149° C.

[2382] R_(f)=0.82 (silica gel; methylene chloride:methanol=95:5)

[2383] HPLC/MS (method D): RT=7,27 min.; [M+H]+=421; Abs. λ max=274 nm

[2384] (55)(3,4-Dichloro-phenyl)-[4-(4,5,7,8-tetrahydro-1H-imidazo[4,5-d]azepin-6-yl)-5-trifluoromethyl-pyrimidine-2-yl]-amine

[2385] Melting point: 247° C. decomposition

[2386] R_(f)=0.19 (silica gel; methylene chloride:methanol=95:5)

[2387] HPLC/MS (method D): RT=5.51 min.; [M+H]+=443; Abs. λ max=274 nm

[2388] (56)(3,4-Dichloro-phenyl)-[4-(2-methyl-4,5,7,8-tetrahydro-1H-imidazo[4,5-d]azepin-6-yl)-5-trifluoromethyl-pyrimidine-2-yl]-amine

[2389] Melting point: 245° C. decomposition

[2390] R_(f)=0.14 (silica gel; methylene chloride:methanol=95:5)

[2391] HPLC/MS (method D): RT=5.59 min.; [M+H]+=459; Abs. λ max=274 nm

[2392] (57)N-(2-{2-[4-(Morpholin-4-sulphonyl)-phenylamino]-5-trifluoromethyl-pyrimidin-4-ylamino}-ethyl)-acetamide

[2393] Melting point: 73-75° C.

[2394] R_(f)=0.19 (silica gel; methylene chloride:methanol=95:5)

[2395] HPLC/MS (method D): RT=5.40 min.; [M−H]−=487; Abs. λ max=277 nm

[2396] (58)N-(2-{2-[4-(4-Methyl-piperazin-1-sulphonyl)-phenylamino]-5-trifluoromethyl-pyrimidin-4-ylamino}-ethyl)-acetamide

[2397] Melting point: 125-127° C.

[2398] R_(f)=0.10 (silica gel; methylene chloride:methanol=95:5)

[2399] HPLC/MS (method D): RT=4,40 min.; [M+H]+=502; Abs. λ max=270 nm

[2400] (59)N-(2-{2-[4-(Pyridin-2-ylsulphamoyl)-phenylamino]-5-trifluoromethyl-pyrimidin-4-ylamino}-ethyl)-acetamide

[2401] Melting point: 228° C.

[2402] R_(f)=0.54 (silica gel; methylene chloride:methanol=95:5)

[2403] HPLC/MS (method D): RT=4,80 min.; [M+H]+=496; Abs. λ max=246 nm

[2404] (60)N-(2-{2-[4-(Perhydro-1,4-diazepin-1-sulphonyl)-phenylamino]-5-trifluoromethyl-pyrimidin-4-ylamino}-ethyl)-acetamide

[2405] Melting point: 167-169° C.

[2406] R_(f)=0.36 (silica gel; methylene chloride:methanol=95:5)

[2407] HPLC/MS (method D): RT=4.40 min.; [M+H]+=502; Abs. λ max=270 nm

[2408] (61)N-(2-{2-[4-(3,5-Dimethyl-piperazin-1-sulphonyl)-phenylamino]-5-trifluoromethyl-pyrimidin-4-ylamino}-ethyl)-acetamide

[2409] Melting point: 117° C.

[2410] R_(f)=0.16 (silica gel; methylene chloride:methanol=95:5)

[2411] HPLC/MS (method D): RT=4,50 min.; [M+H]+=516; Abs. λ max=270 nm

[2412] (62)N-[2-(2-phenylamino-5-trifluoromethylpyrimidin-4-ylamino)-ethyl]-acetamide350 mg of2-chloro-4-(2-acetylamino-ethylamino)-5-trifluoromethyl-pyrimidine and630 mg of4-(4-[tert-butyl-oxycarbonyl]-homopiperazin-1-sulphonyl)-phenylamine aremixed with 3 ml of dioxane and N,N-dimethylformamide is added until allthe components are dissolved. Then 0.25 ml of 4.0M hydrochloric acid in1,4-dioxane are added dropwise and the mixture is heated to 80° C. for 2hours with stirring. Then additional 4.0M hydrochloric acid in1,4-dioxane (1 ml) is added and the mixture is heated to 85° C. for 15minutes. The precipitate formed is filtered off and washed with dioxane.After dissolving in water the solution is purified through an RP C-18column with H₂O/acetonitrile as eluant. After evaporation the product isleft behind as a solid.

[2413] Melting point: 175° C. decomposition

[2414] R_(f)=0.44 (silica gel; methylene chloride:methanol=9:1)

[2415] HPLC/MS (method D): RT=4,605 min.; [M+H]+=340

[2416] (63)4-{5-isopropyl-4-[3-(2-oxo-pyrrolidin-1-yl)-propylamino]-pyrimidin-2-ylamino}-benzamidemelting point: 204-205° C.

[2417] R_(f)=0,13 (silica gel; methylene chloride:methanol=9:1)

[2418] HPLC/MS (method G): RT=2,99 min.; [M+H]+=397; Abs. λ max=279,8 nm

[2419] (64)1-{3-[2-(3-Chloro-4-morpholine-4-yl-phenylamino)-5-trifluoromethyl-pyrimidin-4-ylamino]-propyl}-pyrrolidin-2-onemelting point: 131-134° C.

[2420] R_(f)=0,56 (silica gel; methylene chloride:methanol=9:1)

[2421] HPLC/MS (method G): RT=3,61 min.; [M+H]+=499; Abs. λ max=230 nm

[2422] (65)N-[2-(2-benzylamino-5-trifluoromethyl-pyrimidin-4-ylamino)-ethyl]-acetamidemelting point: 190-191° C.

[2423] R_(f)=0,57 (silica gel; methylene chloride:methanol=9:1)

[2424] HPLC/MS (method G): RT=3,37 min.; [M+H]+=354; Abs. λ max=230 nm

[2425] (66)N-(2-{2-[4-(4-methoxy-piperidin-1-ylmethyl)-phenylamino]-5-trifluoromethyl-pyrimidin-4-ylamino}-ethyl)-acetamide

[2426] (67)N-{2-[2-(3-amino-phenylamino)-5-trifluoromethyl-pyrimidin-4-ylamino]-ethyl}-acetamide

[2427] melting point: 198-200° C.

[2428] R_(f)=0.48 (silica gel; methylene chloride:methanol=9:1)

[2429] HPLC/MS (method F): RT=2,97 min.; [M+H]+=355; Abs. λ max=253 nm

[2430] 1H-NMR(D₆-DMSO, 300 MHz) δ: 1.80 (s, 3H), 3.30 (m, 2H), 3.52 (m,2H), 4.99 (m, 2H), 6.20 (d, 1H), 6.92-6.79 (m, 2H), 7.05 (m, 2H), 7.99(t, 1H), 8.14 (s, 1H), 9.30 (s, 1H).

[2431] (68)4-[4-(4-pyrimidin-2-yl-piperazin-1-yl)-5-trifluoromethyl-pyrimidin-2-ylamino]-benzamidemelting point: 260-262° C.

[2432] R_(f)=0,23 (silica gel; methylene chloride:methanol=9:1)

[2433] HPLC/MS (method G): RT=3,60 min.; [M+H]+=445; Abs. λ max=287,4 nm

[2434] (69)N-{2-[5-isopropyl-2-(4-piperidin-1-ylmethyl-phenylamino)-pyrimidin-4-ylamino]-ethyl}-acetamide

[2435] melting point: 165-168° C.

[2436] R_(f)=0,07 (silica gel; methylene chloride:methanol=4:1)

[2437] HPLC/MS (method F): RT=3,01 min.; [M+H]+=411; Abs. λ max=260,8 nm

[2438](70)1-{3-[5-methoxy-2-(4-piperidin-1-ylmethyl-phenylamino)-pyrimidin-4-ylamino]-propyl}-pyrrolidin-2-one

[2439] R_(f)=0,07 (silica gel; methylene chloride:methanol=4:1)

[2440] HPLC/MS (method F): RT=3,00 min.; [M+H]+=439; Abs. λ max=260,8 nm

[2441] (71)4-{5-dimethylamino-4-[3-(2-oxo-pyrrolidin-1-yl)-propylamino]-pyrimidin-2-ylamino}-benzamide

[2442] melting point: 202-203° C.

[2443] R_(f)=0,14 (silica gel; methylene chloride:methanol=9:1)

[2444] HPLC/MS (method G): RT=2,88 min.; [M+H]+=398; Abs. λ max=295 nm

[2445] (72)4-{4-[4-(2-nitro-phenyl)-piperazin-1-yl]-5-trifluoromethyl-pyrimidin-2-ylamino}-benzamide

[2446] melting point: 223-225° C.

[2447] R_(f)=0,06 (silica gel; methylene chloride:methanol=99:1)

[2448] HPLC/MS (method G): RT=4,45 min.; [M+H]+=488; Abs. λ max=258,9 nm

[2449] (73)N,N-dimethyl-4-[4-(4,5,7,8-tetrahydro-1H-imidazo[4,5-d]azepin-6-yl)-5-trifluoromethyl-pyrimidin-2-ylamino]-phenylsulphonamide

[2450] melting point: 152-155° C.

[2451] R_(f)=0,26 (silica gel; methylene chloride:methanol=95:5)

[2452] HPLC/MS (method D): RT=5,35 min.; [M+H]+=482; Abs. λ max=298 nm

[2453] (74)N-{2-[2-(1H-indazol-6-ylamino)-5-methyl-pyrimidin-4-ylamino]-ethyl}-acetamide

[2454] melting point: 240-243° C.

[2455] R_(f)=0,22 (silica gel; methylene chloride:methanol 4:1)

[2456] HPLC/MS (method F): RT=3,05 min.; [M+H]+=326; Abs. λ max 248 nm

[2457](75)1-{3-[2-(1H-indazol-6-ylamino)-5-methyl-pyrimidin-4-ylamino]-propyl}-pyrrolidin-2-one

[2458] melting point: 227-230° C.

[2459] R_(f)=0,17 (silica gel; methylene chloride:methanol=9:1)

[2460] HPLC/MS (method F): RT=3,24 min.; [M+H]+=366; Abs. ? max=248 nm

[2461] (76)1-(3-{2-[4-(2H-tetrazol-5-yl)-phenylamino]-5-trifluoromethyl-pyrimidin-4-ylamino}-propyl)-pyrrolidin-2-one

[2462] melting point: >300° C. decomposition

[2463] R_(f)=0,06 (silica gel; methylene chloride:methanol=95:5)

[2464] HPLC/MS (method D): RT=5,10 min.; [M+H]+=448; Abs. λ max=236 nm

[2465] (77)N-{2-[2-(4-sulphamoyl-benzylamino)-5-trifluoromethyl-pyrimidin-4-ylamino]-ethyl}-acetamide

[2466] melting point: 205-207° C.

[2467] R_(f)=0,39 (silica gel; methylene chloride:methanol=85:15)

[2468] HPLC/MS (method G): RT=2,31 min.; [M+H]+=433; Abs. λ max=232 nm

[2469] (78)N-{2-[5-Bromo-2-(1H-indazol-6-ylamino)-pyrimidin-4-ylamino]-ethyl}-acetamide

[2470] melting point: 270-272° C.

[2471] R_(f)=0,32 (silica gel; methylene chloride:methanol=9:1)

[2472] HPLC/MS (method F): RT=3,09 min.; [M+H]+=391; Abs. λ max=251 nm

[2473] (79)1-{3-[2-(3-dimethylamino-phenylamino)-5-trifluoromethyl-pyrimidin-4-ylamino]-propyl}-pyrrolidin-2-one

[2474] melting point: 152-155° C.

[2475] R_(f)=0,6 (silica gel; methylene chloride:methanol=9:1)

[2476] HPLC/MS (method G): RT=2,49 min.; [M+H]+=423; Abs. ? max=253 nm

[2477] (80)1-{3-[2-(2,4-dichloro-phenylamino)-5-trifluoromethyl-pyrimidin-4-ylamino]-propyl}-pyrrolidin-2-one

[2478] melting point: 148-150° C.

[2479] R_(f)=0,67 (silica gel; methylene chloride:methanol=9:1)

[2480] HPLC/MS (method G): RT=4,3 min.; [M+H]+=449; Abs. λ max=234 nm

[2481] (81)1-{3-[2-(4-methoxy-2-methyl-phenylamino)-5-trifluoromethyl-pyrimidin-4-ylamino]-propyl}-pyrrolidin-2-one

[2482] melting point: 127-130° C.

[2483] R_(f)=0,58 (silica gel; methylene chloride:methanol=9:1)

[2484] HPLC/MS (method G): RT=3,68 min.; [M+H]+=424; Abs. λ max=236 nm

[2485] (82)1-{3-[2-(2,5-dichloro-phenylamino)-5-trifluoromethyl-pyrimidin-4-ylamino]-propyl}-pyrrolidin-2-one

[2486] R_(f)=0,65 (silica gel; methylene chloride:methanol=9:1)

[2487] HPLC/MS (method I): RT=3,66 min.; [M+H]+=449; Abs. λ max=244 nm

[2488] (83)1-{3-[2-(3-fluoro-5-trifluoromethyl-phenylamino)-5-trifluoromethyl-pyrimidin-4-ylamino]-propyl}-pyrrolidin-2-one

[2489] melting point: 183-184° C.

[2490] R_(f)=0,6 (silica gel; methylene chloride:methanol=9:1)

[2491] HPLC/MS (method I): RT=4,07 min.; [M+H]+=466; Abs. λ max=257 nm

[2492] (84)1-3-[2-(2-fluoro-5-trifluoromethyl-phenylamino)-5-trifluoromethyl-pyrimidin-4-ylamino]-propyl}-pyrrolidin-2-one

[2493] melting point: 148-149° C.

[2494] R_(f)=0,65 (silica gel; methylene chloride:methanol=91:1)

[2495] HPLC/MS (method I): RT=3,51 min.; [M+H]+=466; Abs. λ max=244 nm

[2496] (85)N-{2-[2-(3-Bromo-benzylamino)-5-trifluoromethyl-pyrimidin-4-ylamino]-ethyl}-acetamide

[2497] melting point: 162-165° C.

[2498] R_(f)=0.44 (silica gel; methylene chloride:methanol=9:1)

[2499] HPLC/MS (method G): RT=3,65 min.; [M+H]+=433; Abs. λ max=236 nm

[2500] (86)N-{2-[2-(1-phenyl-ethylamino)-5-trifluoromethyl-pyrimidin-4-ylamino]-ethyl}-acetamide

[2501] melting point: 125-140° C.

[2502] R_(f)=0.46 (silica gel; methylene chloride:methanol=9:1)

[2503] HPLC/MS (method F): RT=3,53 min.; [M+H]+=368; Abs. λ max=230 nm

[2504] (87)1-{3-[2-(2-isopropyl-phenylamino)-5-trifluoromethyl-pyrimidin-4-ylamino]-propyl}-pyrrolidin-2-one

[2505] melting point: 115-118° C.

[2506] R_(f)=0,26 (silica gel; methylene chloride:methanol=9:1)

[2507] HPLC/MS (method G): RT=3,94 min.; [M+H]+=422; Abs. λ max=232 nm

[2508] (88)1-{3-[2-(Biphenyl-4-ylamino)-5-trifluoromethyl-pyrimidin-4-ylamino]-propyl}-pyrrolidin-2-one

[2509] melting point: 155-156° C.

[2510] R_(f)=0,74 (silica gel; methylene chloride:methanol=9:1)

[2511] HPLC/MS (method H): RT=4,07 min.; [M+H]+=456; Abs. λ max=242 nm

[2512] (89)1-{3-[2-(2,4-Difluoro-phenylamino)-5-trifluoromethyl-pyrimidin-4-ylamino]-propyl}-pyrrolidin-2-one

[2513] melting point: 117-120° C.

[2514] R_(f)=0,76 (silica gel; methylene chloride:methanol=8:2)

[2515] HPLC/MS (method G): RT=3,76 min.; [M+H]+=416; Abs. λ max=238 nm

[2516] (90)1-{3-[2-(2-Chloro-4-methyl-phenylamino)-5-trifluoromethyl-pyrimidin-4-ylamino]-propyl}-pyrrolidin-2-one

[2517] melting point: 110-113° C.

[2518] R_(f)=0,71 (silica gel; methylene chloride:methanol=9:1)

[2519] HPLC/MS (method G): RT=4,02 min.; [M+H]+=428; Abs. λ max=242 nm

[2520](91)1-{3-[2-(2-Chloro-5-trifluoromethyl-phenylamino)-5-trifluoromethyl-pyrimidin-4-ylamino]-propyl}-pyrrolidin-2-one

[2521] melting point: 139-140° C.

[2522] R_(f)=0,77 (silica gel; methylene chloride:methanol=9:1)

[2523] HPLC/MS (method H): RT=4,51 min.; [M+H]+=482; Abs. λ max=248 nm

[2524] (92)1-{3-[2-(3,5-Difluoro-phenylamino)-5-trifluoromethyl-pyrimidin-4-ylamino]-propyl}-pyrrolidin-2-one

[2525] melting point: 210-212° C.

[2526] R_(f)=0,71 (silica gel; methylene chloride:methanol=9:1)

[2527] HPLC/MS (method G): RT=4,32 min.; [M+H]+=416; Abs. λ max=253 nm

[2528] (93)N-{2-[2-(3,4-dichloro-benzylamino)-5-trifluoromethyl-pyrimidin-4-ylamino]-ethyl}-acetamide

[2529] melting point: 168° C.

[2530] R_(f)=0,57 (silica gel; methylene chloride:methanol=9:1)

[2531] HPLC/MS (method G): RT=3,79 min.; [M+H]+=422; Abs. λ max=230 nm

[2532](94)1-{3-[5-trifluoromethyl-2-(2-trifluoromethyl-phenylamino)-pyrimidin-4-ylamino]-propyl}-pyrrolidin-2-one

[2533] R_(f)=0,65 (silica gel; methylene chloride:methanol=9:1)

[2534] HPLC/MS (method H): RT=3,29 min.; [M+H]+=448; Abs. λ max=234 nm

[2535] (95)1-{3-[2-(4-isopropyl-phenylamino)-5-trifluoromethyl-pyrimidin-4-ylamino]-propyl}-pyrrolidin-2-one

[2536] melting point: 124-126° C.

[2537] R_(f)=0,62 (silica gel; methylene chloride:methanol=9:1)

[2538] HPLC/MS (method H): RT=3,75 min.; [M+H]+=422; Abs. λ max=259 nm

[2539] (96)1-{3-[2-(4-dimethylamino-phenylamino)-5-trifluoromethyl-pyrimidin-4-ylamino]-propyl}-pyrrolidin-2-one

[2540] melting point: 156-158° C.

[2541] R_(f)=0,54 (silica gel; methylene chloride:methanol=9:1)

[2542] HPLC/MS (method F): RT=3,25 min.; [M+H]+=423; Abs. λ max=257 nm

[2543] (97)1-{3-[2-(4-morpholin-4-yl-phenylamino)-5-trifluoromethyl-pyrimidin-4-ylamino]-propyl}-pyrrolidin-2-one

[2544] melting point: 115-118° C.

[2545] R_(f)=0,52 (silica gel; methylene chloride:methanol=9:1)

[2546] HPLC/MS (method H): RT=3,25 min.; [M+H]+=465; Abs. λ max=257 nm

[2547] (98)N-{2-[2-(4-dimethylsulphamoyl-phenylamino)-5-methyl-pyrimidin-4-ylamino]-ethyl}-acetamide

[2548] melting point: 204-206° C.

[2549] R_(f)=0,3 (silica gel; methylene chloride:methanol=9:1)

[2550] HPLC/MS (method F): RT=3,15 min.; [M+H]+=393; Abs. λ max=282 nm

[2551] (99)4-[5-Chloro-4-(4,5,7,8-tetrahydro-1H-imidazo[4,5-d]azepin-6-yl)-pyrimidin-2-ylamino]-N,N-dimethyl-phenylsulphonamide

[2552] melting point: 160-162° C.

[2553] R_(f)=0,22 (silica gel; methylene chloride:methanol=9:1)

[2554] HPLC/MS (method F): RT=3,79 min.; [M+H]+=448; Abs. λ max=286 nm

[2555] (100)4-{5-Bromo-4-[3-(2-oxo-pyrrolidin-1-yl)-propylamino]-pyrimidin-2-ylamino}-N,N-dimethyl-phenylsulphonamide

[2556] melting point: 165,1-167,7° C.

[2557] R_(f)=0,51 (silica gel; methylene chloride:methanol 9:1)

[2558] HPLC/MS (method F): RT=3,85 min.; [M+H]+=498; Abs. λ max=284 nm

[2559] (101)N-{2-[5-Chloro-2-(4-dimethylsulphamoyl-phenylamino)-pyrimidin-4-ylamino]-ethyl}-acetamide

[2560] melting point: >300° C. decomposition

[2561] R_(f)=0.42 (silica gel; methylene chloride:methanol=9:1)

[2562] HPLC/MS (method F): RT=3,58 min.; [M+H]+=413; Abs. λ max=284 nm

[2563] (102)N-{2-[5-Bromo-2-(4-piperidin-1-ylmethyl-phenylamino)-pyrimidin-4-ylamino]-ethyl}-acetamide

[2564] melting point: 154-157° C.

[2565] R_(f)=0,1 (silica gel; methylene chloride:methanol=9:1)

[2566] HPLC/MS (method F): RT=2,7 min.; [M+H]+=448; Abs. λ max=253 nm

[2567](103)1-{3-[5-Bromo-2-(4-piperidin-1-ylmethyl-phenylamino)-pyrimidin-4-ylamino]-propyl}-pyrrolidin-2-one

[2568] melting point: 137-138° C.

[2569] R_(f)=0,25 (silica gel; methylene chloride:methanol=9:1)

[2570] HPLC/MS (method F): RT=3,16 min.; [M+H]+=488; Abs. λ max=268 nm

[2571] (104)N-{2-[5-methyl-2-(4-piperidin-1-ylmethyl-phenylamino)-pyrimidin-4-ylamino]-ethyl}-acetamide

[2572] melting point: 150-152° C.

[2573] R_(f)=0,06 (silica gel; methylene chloride:methanol=4:1)

[2574] HPLC/MS (method F): RT=2,52 min.; [M+H]+=383; Abs. λ max=263 nm

[2575] (105)N,N-dimethyl-4-{5-methyl-4-[3-(2-oxo-pyrrolidin-1-yl)-propylamino]-pyrimidin-2-ylamino}-phenylsulphonamide

[2576] melting point: 186-189° C.

[2577] R_(f)=0.41 (silica gel; methylene chloride:methanol=9:1)

[2578] HPLC/MS (method F): RT=3,6 min.; [M+H]+=433; Abs. λ max=282 nm

[2579](106)1-{3-[5-Bromo-2-(1H-indazol-6-ylamino)-pyrimidin-4-ylamino]-propyl}-pyrrolidin-2-one

[2580] melting point: 211-213° C.

[2581] R_(f)=0.44 (silica gel; methylene chloride:methanol=9:1)

[2582] HPLC/MS (method F): RT=3,62 min.; [M+H]+=431; Abs. λ max=251 nm

[2583] (107)N-{2-[2-(2-fluoro-benzylamino)-5-trifluoromethyl-pyrimidin-4-ylamino]-ethyl}-acetamide

[2584] melting point: 188-189° C.

[2585] R_(f)=0.44 (silica gel; methylene chloride:methanol=9:1)

[2586] HPLC/MS (method G): RT=3,34 min.; [M+H]+=372; Abs. λ max=229 nm

[2587] (108)N-(2-{2-[1-(4-Bromo-phenyl)-ethylamino]-5-trifluoromethyl-pyrimidin-4-ylamino}-ethyl)-acetamide

[2588] melting point: 143-145° C.

[2589] R_(f)=0.46 (silica gel; methylene chloride:methanol=9:1)

[2590] HPLC/MS (method H): RT=3,29 min.; [M+H]+=447; Abs. λ max=230 nm

[2591] (109)4-{5-Chloro-4-[3-(2-oxo-pyrrolidin-1-yl)-propylamino]-pyrimidin-2-ylamino}-N,N-dimethyl-phenylsulphonamide

[2592] melting point: 159-161° C.

[2593] R_(f)=0,53 (silica gel; methylene chloride:methanol=9:1)

[2594] HPLC/MS (method F): RT=3,55 min.; [M+H]+=453; Abs. λ max=284 nm

[2595](110)1-{3-[5-Chloro-2-(4-piperidin-1-ylmethyl-phenylamino)-pyrimidin-4-ylamino]-propyl}-pyrrolidin-2-one

[2596] melting point: 137-138° C.

[2597] R_(f)=0,20 (silica gel; methylene chloride:methanol=9:1)

[2598] HPLC/MS (method F): RT=3,21 min.; [M+H]+=443; Abs. ? max=267 nm

[2599] (111)4-[4-(2-acetylamino-ethylamino)-5-dimethylamino-pyrimidin-2-ylamino]-benzamide

[2600] melting point: 218-220° C.

[2601] R_(f)=0.46 (silica gel; methylene chloride:methanol=4:1)

[2602] HPLC/MS (method G): RT=2,63 min.; [M+H]+=358; Abs. λ max=293,1 nm

[2603] (112)4-[4-(2-acetylamino-ethylamino)-5-isopropyl-pyrimidin-2-ylamino]-benzamide

[2604] melting point: 229° C.

[2605] R_(f)=0.42 (silica gel; methylene chloride:methanol=4:1)

[2606] HPLC/MS (method G): RT=2,77 min.; [M+H]+=357; Abs. λ max=285,5 nm

[2607] (113)4-{5-methanesulphonyl-4-[3-(2-oxo-pyrrolidin-1-yl)-propylamino]-pyrimidin-2-ylamino}-benzamide

[2608] melting point: 244-246° C.

[2609] R_(f)=0,07 (silica gel; methylene chloride:methanol=99:1)

[2610] HPLC/MS (method F): RT=3,15 min.; [M+H]+=433; Abs. λ max=287,4 nm

[2611](114)1-{3-[2-(3,4-dichloro-phenylamino)-5-methylsulphonyl-pyrimidin-4-ylamino]-propyl}-pyrrolidin-2-one

[2612] melting point: 200-203° C.

[2613] R_(f)=0.48 (silica gel; methylene chloride:methanol=99:1)

[2614] HPLC/MS (method G): RT=4,34 min.; [M+H]+=459; Abs. λ max=262,7 nm

[2615] (115)4-[5-dimethylamino-4-(4-pyridin-2-yl-piperazin-1-yl)-pyrimidin-2-ylamino]-benzamide

[2616] melting point: 237-238° C.

[2617] R_(f)=0,20 (silica gel; methylene chloride:methanol=9:1)

[2618] HPLC/MS (method G): RT=2,69 min.; [M+H]+=419; Abs. λ max=298,8 nm

[2619] (116)1-{3-[2-(3,4-dichloro-phenylamino)-5-isopropyl-pyrimidin-4-ylamino]-propyl}-pyrrolidin-2-one

[2620] melting point: 147-150° C.

[2621] R_(f)=0,08 (silica gel; methylene chloride:methanol=99:1)

[2622] HPLC/MS (method G): RT=4,00 min.; [M+H]+=423; Abs. λ max=264,6 nm

[2623] (117)4-{5-methoxy-4-[3-(2-oxo-pyrrolidin-1-yl)-propylamino]-pyrimidin-2-ylamino}-benzamide

[2624] melting point: 212-213° C.

[2625] R_(f)=0,12 (silica gel; methylene chloride:methanol=9:1)

[2626] HPLC/MS (method G): RT=2,74 min.; [M+H]+=385; Abs. λ max=291,2 nm

[2627](118)1-{3-[2-(3,4-dichloro-phenylamino)-5-methoxy-pyrimidin-4-ylamino]-propyl}-pyrrolidin-2-one

[2628] melting point: 148-150° C.

[2629] R_(f)=0,05 (silica gel; methylene chloride:methanol=99:1)

[2630] HPLC/MS (method H): RT=3,39 min.; [M+H]+=411; Abs. λ max=264,6 nm

[2631] (119)N-{2-[5-methoxy-2-(4-piperidin-1-ylmethyl-phenylamino)-pyrimidin-4-ylamino]-ethyl}-acetamide

[2632] melting point: 109-111° C.

[2633] R_(f)=0,09 (silica gel; methylene chloride:methanol=4:1)

[2634] HPLC/MS (method F): RT=2,89 min.; [M+H]+=399; Abs. λ max=257 nm

[2635] (120)[5-methoxy-4-(4-pyridin-2-yl-piperazin-1-yl)-pyrimidin-2-yl]-(4-piperidin-1-ylmethyl-phenyl)-amine

[2636] melting point: 158-159° C.

[2637] R_(f)=0,12 (silica gel; methylene chloride:methanol=9:1)

[2638] HPLC/MS (method F): RT=2,92 min.; [M+H]+=460; Abs. λ max=266,5 nm

[2639] (121)N-{2-[5-dimethylamino-2-(4-piperidin-1-ylmethyl-phenylamino)-pyrimidin-4-ylamino]-ethyl}-acetamide

[2640] R_(f)=0,08 (silica gel; methylene chloride:methanol=4:1)

[2641] HPLC/MS (method F): RT=2,94 min.; [M+H]+=412; Abs. λ max=257 nm

[2642] (122)1-{3-[2-(3,4-dichloro-phenylamino)-5-dimethylamino-pyrimidin-4-ylamino]-propyl}-pyrrolidin-2-one

[2643] melting point: 103-106° C.

[2644] R_(f)=0,22 (silica gel; methylene chloride:methanol=99:1)

[2645] HPLC/MS (method G): RT=3,87 min.; [M+H]+=424; Abs. λ max=268,4 nm

[2646] (123)[5-isopropoxy-4-(4-pyridin-2-yl-piperazin-1-yl)-pyrimidin-2-yl]-(4-piperidin-1-ylmethyl-phenyl)-amine

[2647] melting point: 143-145° C.

[2648] R_(f)=0,13 (silica gel; methylene chloride:methanol=9:1)

[2649] HPLC/MS (method F): RT=3,06 min.; [M+H]+=488; Abs. λ max=272,2 nm

[2650](124)1-{3-[5-isopropoxy-2-(4-piperidin-1-ylmethyl-phenylamino)-pyrimidin-4-ylamino]-propyl}-pyrrolidin-2-one

[2651] R_(f)=0,13 (silica gel; methylene chloride:methanol=9:1)

[2652] HPLC/MS (method F): RT=3,21 min.; [M+H]+=467; Abs. λ max=253,2 nm

[2653] (125)N-{2-[5-isopropoxy-2-(4-piperidin-1-ylmethyl-phenylamino)-pyrimidin-4-ylamino]-ethyl}-acetamide

[2654] melting point: 105-107° C.

[2655] R_(f)=0,06 (silica gel; methylene chloride:methanol=9:1)

[2656] HPLC/MS (method F): RT=3,06 min.; [M+H]+=427; Abs. λ max=255,1 nm

[2657] (126)N-{2-[2-(3,4-dichloro-phenylamino)-5-isopropyl-pyrimidin-4-ylamino]-ethyl}-acetamide

[2658] melting point: 206-207° C.

[2659] R_(f)=0,18 (silica gel; methylene chloride:methanol=99:1)

[2660] HPLC/MS (method G): RT=3,70 min.; [M+H]+=383; Abs. λ max=264,6 nm

[2661] (127)N-{2-[2-(3,4-dichloro-phenylamino)-5-dimethylamino-pyrimidin-4-ylamino]-ethyl}-acetamide

[2662] melting point: 165-168° C.

[2663] R_(f)=0,05 (silica gel; methylene chloride:methanol=99:1)

[2664] HPLC/MS (method G): RT=3,57 min.; [M+H]+=384; Abs. λ max=264,6 nm

[2665] (128)N-(2-[2-(4-amino-phenylamino)-5-trifluoromethyl-pyrimidin-4-ylamino]-ethyl)-acetamide

[2666] 3 g ofN-[2-(2-chloro-5-trifluoromethyl-pyrimidin-4-ylamino)-ethyl]-acetamideare combined with 6.9 g of p-phenylenediamine in 25 ml of glacial aceticacid and stirred for 4 hours at ambient temperature. After removal ofthe acetic acid in vacuo the reaction mixture is taken up indichloromethane and washed with saturated sodium carbonate solution. Theaqueous phase is extracted with dichloromethane. The combined organicphases are dried over sodium sulphate and evaporated down. The crudeproduct is purified by chromatography (silica gel, CH₂Cl₂/iPrOH=20/1).3.0 g of a grey solid are obtained.

[2667] R_(f) (CH₂Cl₂/iPrOH=8/2+1% NH₃; SiO₂)=0.35

[2668] 1H-NMR(D₆-DMSO, 300 MHz) δ: 1.80 (s, 3H), 3.25 (m, 2H), 3.47 (m,2H), 4.78 (m, 2H), 6.50 (d, 1H), 6.93 (m, 1H), 7.29 (d, 2H), 7.90 (t,1H), 8.08 (s, 1H), 9.13 (s, 1H).

[2669](129)1-{3-[5-isopropyl-2-(4-piperidin-1-ylmethyl-phenylamino)-pyrimidin-4-ylamino]-propyl}-pyrrolidin-2-one

[2670] melting point: 142-144° C.

[2671] R_(f)=0,05 (silica gel; methylene chloride:methanol=9:1)

[2672] HPLC/MS (method F): RT=3,2 min.; [M+H]+=451; Abs. λ max=253,2 nm

[2673] (130)N-{2-[2-(4-methylamino-phenylamino)-5-trifluoromethyl-pyrimidin-4-ylamino]-ethyl}-acetamide

[2674] The compound is prepared fromN-tert-butyl-oxycarbonyl-N-methyl-amino-4-aminobenzene and Example II.The intermediate product is combined with 5 eq. of 4.0M hydrochloricacid in 1,4-dioxane and heated to 85° C. for 0.5 hours with stirring.After elimination of the solvent in vacuo the crude product is taken upin dichloromethane and purified by chromatography (silica gel,CH₂Cl₂/methanol).

[2675] melting point: 169-171° C.

[2676] R_(f)=0,37 (silica gel; methylene chloride:methanol=9:1)

[2677] HPLC/MS (method F): RT=2,96 min.; [M+H]+=369; Abs. λ max=257 nm

[2678] (131)N-{2-[2-(3-methylamino-phenylamino)-5-trifluoromethyl-pyrimidin-4-ylamino]-ethyl}-acetamide

[2679] Prepared analogously to 2(130).

[2680] melting point: 191-193° C.

[2681] R_(f)=0.49 (silica gel; methylene chloride:methanol=9:1)

[2682] HPLC/MS (method G): RT=2,68 min.; [M+H]+=369; Abs. λ max=253 nm

[2683] (132)N-{2-[2-(3-formyl-phenylamino)-5-trifluoromethyl-pyrimidin-4-ylamino]-ethyl}-acetamide

[2684] 12 g of manganese dioxide are suspended in 200 ml ofdichloromethane, cooled to 0° C. and a solution ofN-{2-[2-(3-hydroxymethyl-phenylamino)-5-trifluoromethyl-pyrimidin-4-ylamino]-ethyl}-acetamide(prepared analogously to 2(52)) in 300 ml of THF is slowly added at 0°C. The reaction mixture is heated to ambient temperature and stirred for6 h. After the reaction mixture has been filtered the filter cake isthoroughly washed with THF and the solution is evaporated down. Theresidue is taken up in ethyl acetate and after treatment in theultrasound bath filtered again. The procedure is repeated withethylether and finally a white solid is obtained in a 70% yield.

[2685] R_(f)=0.40 (silica gel; methylene chloride:methanol=20:1)

[2686] 1H-NMR (D6-DMSO, 300 MHz) δ: 1.81 (s, 3H), 3.30 (m, 2H), 3.55 (m,2H), 7.30 (m, 1H), 7.82 (m, 2H), 7.96 (m, 4H), 8.25 (s, 1H), 9.82 (s,1H), 10.11 (s, 1H).

[2687] (133)N-{2-[2-(4-formyl-phenylamino)-5-trifluoromethyl-pyrimidin-4-ylamino]-ethyl}-acetamide

[2688]N-{2-[2-(4-formyl-phenylamino)-5-trifluoromethyl-pyrimidin-4-ylamino]-ethyl}-acetamideis obtained analogously to 2(132) fromN-{2-[2-(4-hydroxymethyl-phenylamino)-5-trifluoromethyl-pyrimidin-4-ylamino]-ethyl}-acetamide(prepared analogously to 2(52)) in a 76% yield.

[2689] R_(f)=0.35 (silica gel; methylene chloride:methanol=20:1)

[2690] HPLC/MS (method F): RT=3.48 min.; [M+H]+=368

[2691] 1H-NMR (D6-DMSO, 300 MHz) δ: 1.80 (s, 3H), 3.31 (m, 2H), 3.57 (m,2H), 7.22 (m, 1H), 7.51 (m, 2H), 7.91 (m, 3H), 8.21 (s, 1H), 8.42 (s,1H), 9.90 (s, 1H), 9.93 (s, 1H).

[2692] (134)[5-Chloro-4-(1,4,6,7-tetrahydro-imidazo[4,5-c]pyridin-5-yl)-pyrimidin-2-yl]-(1H-indazol-6-yl)-amine

[2693] melting point: >300° C. decomposition

[2694] R_(f)=0.42 (silica gel; methylene chloride:methanol=4:1)

[2695] HPLC/MS (method F): RT=3,09 min.; [M+H]+=367; Abs. λ max=282 nm

[2696] (135)(1H-indazol-6-yl)-[5-methyl-4-(4,5,7,8-tetrahydro-1H-imidazo[4,5-d]azepin-6-yl)-pyrimidin-2-yl]-amine

[2697] melting point: >300° C. decomposition

[2698] R_(f)=0,08 (silica gel; methylene chloride:methanol=4:1)

[2699] HPLC/MS (method F): RT=2,92 min.; [M+H]+=361; Abs. λ max=246 nm

[2700] (136)4-[5-Chloro-4-(1,4,6,7-tetrahydro-imidazo[4,5-c]pyridin-5-yl)-pyrimidin-2-ylamino]-N,N-dimethyl-phenylsulphonamide

[2701] melting point: 171-173° C.

[2702] R_(f)=0,29 (silica gel; methylene chloride:methanol=9:1)

[2703] HPLC/MS (method F): RT=3,71 min.; [M+H]+=434; Abs. λ max=291 nm

[2704] (137)[5-Chloro-4-(4,5,7,8-tetrahydro-1H-imidazo[4,5-d]azepin-6-yl)-pyrimidin-2-yl]-(1H-indazol-6-yl)-amine

[2705] melting point: >290° C. decomposition

[2706] R_(f)=0,19 (silica gel; methylene chloride:methanol=4:1)

[2707] HPLC/MS (method F): RT=3,03 min.; [M+H]+381; Abs. λ max=282 nm

[2708] (138)(1H-indazol-6-yl)-[5-methyl-4-(1,4,6,7-tetrahydro-imidazo[4,5-c]pyridin-5-yl)-pyrimidin-2-yl]-amine

[2709] melting point: >320° C. decomposition

[2710] R_(f)=0,3 (silica gel; methylene chloride:methanol=8:2)

[2711] HPLC/MS (method F): RT=2,87 min.; [M+H]+=; 347 Abs. λ max=251 nm

[2712] (139)[5-methoxy-4-(1,4,6,7-tetrahydro-imidazo[4,5-c]pyridin-5-yl)-pyrimidin-2-yl]-(4-piperidin-1-ylmethyl-phenyl)-amine

[2713] melting point: 105-108° C.

[2714] R_(f)=0,06 (silica gel; methylene chloride:methanol=4:1)

[2715] HPLC/MS (method F): RT=2,83 min.; [M+H]+=420; Abs. λ max=268,4 nm

[2716] (140)(3,4-dichloro-phenyl)-[5-methoxy-4-(1,4,6,7-tetrahydro-imidazo[4,5-c]pyridin-5-yl)-pyrimidin-2-yl]-amine

[2717] R_(f)=0,13 (silica gel; methylene chloride:methanol=9:1)

[2718] HPLC/MS (method G): RT=3,22 min.; [M+H]+=392; Abs. λ max=272,2 nm

[2719] (141)[5-Bromo-4-(4,5,7,8-tetrahydro-1H-imidazo[4,5-d]azepin-6-yl)-pyrimidin-2-yl]-(1H-indazol-6-yl)-amine

[2720] melting point: 258-260° C.

[2721] R_(f)=0,22 (silica gel; methylene chloride:methanol=9:1)

[2722] HPLC/MS (method F): RT=3,05 min.; [M+H]+=426; Abs. ? max=283 nm

[2723] (142)[5-Bromo-4-(1,4,6,7-tetrahydro-imidazo[4,5-c]pyridin-5-yl)-pyrimidin-2-yl]-(1H-indazol-6-yl)-amine

[2724] melting point: >300° C. decomposition

[2725] R_(f)=0,2 (silica gel; methylene chloride:methanol=9:1)

[2726] HPLC/MS (method F): RT=3,12 min.; [M+H]+=412; Abs. λ max=255 nm

[2727] (143)N,N-dimethyl-4-[5-methyl-4-(1,4,6,7-tetrahydro-imidazo[4,5-c]pyridin-5-yl)-pyrimidin-2-ylamino]-phenylsulphonamide

[2728] melting point: 228-230° C.

[2729] R_(f)=0,27 (silica gel; methylene chloride:methanol=9:1)

[2730] HPLC/MS (method F): RT=3,14 min.; [M+H]+=414; Abs. λ max=282 nm

[2731] (144)N,N-dimethyl-4-[5-methyl-4-(4,5,7,8-tetrahydro-1H-imidazo[4,5-d]azepin-6-yl)-pyrimidin-2-ylamino]-phenylsulphonamide

[2732] melting point: 173-176° C.

[2733] R_(f)=0,2 (silica gel; methylene chloride:methanol=9:1)

[2734] HPLC/MS (method F): RT=3,04 min.; [M+H]+=428; Abs. λ max=256 nm

[2735] (145)N⁵,N⁵-dimethyl-N⁵-(4-piperidin-1-ylmethyl-phenyl)-4-(1,4,6,7-tetrahydro-imidazo[4,5-c]pyridin-5-yl)-pyrimidine-2,5-diamine

[2736] melting point: 126-129° C.

[2737] R_(f)=0,08 (silica gel; methylene chloride:methanol=4:1)

[2738] HPLC/MS (method F): RT=2,89 min.; [M+H]+=433; Abs. λ max=257 nm

[2739] (146)[5-isopropyl-4-(1,4,6,7-tetrahydro-imidazo[4,5-c]pyridin-5-yl)-pyrimidin-2-yl]-(4-piperidin-1-ylmethyl-phenyl)-amine

[2740] melting point: 234-237° C.

[2741] R_(f)=0,13 (silica gel; methylene chloride:methanol=9:1)

[2742] HPLC/MS (method F): RT=2,95 min.; [M+H]+=432; Abs. λ max=266,5 nm

[2743] (147)N-{2-[2-(3,4-dichloro-phenylamino)-5-methanesulphonyl-pyrimidin-4-ylamino]-ethyl}-acetamide

[2744] melting point: 245-248° C.

[2745] R_(f)=0,36 (silica gel; methylene chloride:methanol=9:1)

[2746] HPLC/MS (method F): RT=4,15 min.; [M+H]+=419; Abs. λ max=276 nm

[2747] (148)N-2-{5-methyl-2-[3-(2,2,2-trifluoroethyl)-2,3,4,5-tetrahydro-1H-benzo[d]azepin-7-ylamino]-pyrimidin-4-ylamino}-ethyl)-acetamide

[2748] Melting point: 154-156° C.

[2749] R_(f)=0.27 (silica gel; methylene chloride:methanol=9:1)

[2750] HPLC/MS (method D): RT=2.12 min.; [M+H]+=437; Abs./max=253 nm

[2751] (149)N-2-{5-chloro-2-[3-(2,2,2-trifluoroethyl)-2,3,4,5-tetrahydro-1H-benzo[d]azepin-7-ylamino]-pyrimidin-4-ylamino}-ethyl)-acetamide

[2752] Melting point: 205-208° C.

[2753] R_(f)=0.44 (silica gel; methylene chloride:methanol=9:1)

[2754] HPLC/MS (method D): RT=3.07 min.; [M+H]+=457; Abs./max=263 nm

[2755](150)1-(3-{2-[3-(2,2,2-trifluoroethyl)-2,3,4,5-tetrahydro-1H-benzo[d]azepin-7-ylamino]-5-trifluoromethyl-pyrimidin-4-ylamino}-propyl)-pyrrolidin-2-one

[2756] Melting point: 132-133° C.

[2757] R_(f)=0.62 (silica gel; methylene chloride:methanol=9:1)

[2758] HPLC/MS (method F): RT=2.95 min.; [M+H]+=531; Abs./max=259 nm

[2759] (151)N-2-{5-bromo-2-[3-(2,2,2-trifluoroethyl)-2,3,4,5-tetrahydro-1H-benzo[d]azepin-7-ylamino]-pyrimidin-4-ylamino}-ethyl)-acetamide

[2760] Melting point: 186-191° C.

[2761] R_(f)=0.44 (silica gel; methylene chloride:methanol=9:1)

[2762] HPLC/MS (method D): RT=3.12 min.; [M+H]+=502; Abs./max=267 nm

[2763](152)1-(3-{5-methyl-2-[3-(2,2,2-trifluoroethyl)-2,3,4,5-tetrahydro-1H-benzo[d]azepin-7-ylamino]-pyrimidin-4-ylamino}-propyl)-pyrrolidin-2-one

[2764] Melting point: oil

[2765] R_(f)=0.38 (silica gel; methylene chloride:methanol=9:1)

[2766] HPLC/MS (method D): RT=3.67 min.; [M+H]+=477; Abs./max=259 nm

[2767] (153)1-(3-{5-chloro-2-[3-(2,2,2-trifluoroethyl)-2,3,4,5-tetrahydro-1H-benzo[d]azepin-7-ylamino]-pyrimidin-4-ylamino}-propyl)-pyrrolidin-2-one

[2768] Melting point: 57-75° C.

[2769] R_(f)=0.79 (silica gel; methylene chloride:methanol=8:2)

[2770] HPLC/MS (method D): RT=3.70 min.; [M+H]+=497; Abs./max=265 nm

[2771] (154)1-(3-{5-bromo-2-[3-(2,2,2-trifluoroethyl)-2,3,4,5-tetrahydro-1H-benzo[d]azepin-7-ylamino]-pyrimidin-4-ylamino}-propyl)-pyrrolidin-2-one

[2772] Melting point: 138-144° C.

[2773] R_(f)=0.55 (silica gel; methylene chloride:methanol=8:2)

[2774] HPLC/MS (method D): RT=3.71 min.; [M+H]+=542; Abs./max=263 nm

EXAMPLE 3

[2775]N-{2-[2-(3,4-Dichloro-phenylamino)-5-trimethylsilanylethynyl-pyrimidin-4-ylamino]-ethyl}-acetamidHydrochlorid

[2776] Analogously to Example 2, 229 mg ofN-{2-[2-(3,4-dichloro-phenylamino)-5-trimethylsilanylethynyl-pyrimidin-4-ylamino]-ethyl}-acetamidehydrochloride were obtained from 104 mg of 3,4-dichloroaniline and 200mg ofN-[2-(2-chloro-5-trimethylsilanylethynyl-pyrimidin-4-ylamino)-ethyl]acetamide(Example II(10)).

[2777] Melting point: 206-208° C.

[2778] Rf (ethyl acetate; SiO2)=0.51

[2779] RT (HPLC, Method D)=7.29 min., UVmax=286 nm

[2780] The following compound was obtained analogously to Example 3:

[2781]N-{2-[2-(4-Dimethylsulphamoyl-phenylamino)-5-trimethylsilanylethynyl-pyrimidin-4-ylamino]-ethyl}-acetamidehydrochloride

EXAMPLE 4

[2782]N-{2-[2-(3,4-dichloro-phenylamino)-5-ethynyl-pyrimidin-4-ylamino]-ethyl}-acetamide145 mg of tetrabutylammonium fluoride×3H₂O is dissolved in 10 ml ofmethanol and combined with 100 mg ofN-{2-[2-(3,4-dichloro-phenylamino)-5-trimethylsilanylethynyl-pyrimidin-4-ylamino]-ethyl}-acetamide,homogenised in an ultrasound bath and stirred overnight at RT.

[2783] The mixture is then evaporated down in vacuo and filtered throughsilica gel with methanol/dichloromethane (1/10). 54 mg ofN-{2-[2-(3,4-dichloro-phenylamino)-5-ethynyl-pyrimidin-4-ylamino]-ethyl}-acetamideis isolated in a 64% yield.

[2784] Melting point: 221-224° C.

[2785] Rf (ethyl acetate/SiO2)=0.32

[2786] RT (HPLC, method D)=5.30 min., UVmax=282 nm The followingcompound was obtained analogously to Example 4:

[2787] 4(1)N-{2-[2-(4-dimethylsulphamoyl-phenylamino)-5-ethynyl-pyrimidin-4-ylamino]-ethyl}-acetamide

[2788] Melting point: 179-185° C.

[2789] Rf (ethyl acetate/SiO2)=0.14

[2790] RT (HPLC, method D)=4.71 min., UVmax=294 nm

EXAMPLE 5

[2791]N-{2-[2-(4-dimethylsulphamoyl-phenylamino)-5-ethyl-pyrimidin-4-ylamino]-ethyl}-acetamidehydrochloride

[2792] 50 mg ofN-{2-[2-(3,4-dichloro-phenylamino)-5-ethynyl-pyrimidin-4-ylamino]-ethyl}-acetamideare dissolved in 15 ml of ethanol and 15 ml of ethyl acetate andcombined with 25 mg of Pd/C (5%). The mixture is hydrogenated in theshaking autoclave at ambient temperature and 3.5 bar (50 psi) for 3.5hours.

[2793] Then the catalyst is filtered off, the solution is combined withHCl in dioxane and evaporated down. The product is obtained in a 50 mgyield.

[2794] Melting point: >219° C. decomposition

[2795] Rf (ethyl acetate/SiO2)=0.39

[2796] RT (HPLC, method D)=4.37 min., UVmax=282 nm

EXAMPLE 6

[2797]4-[4-(2-acetylamino-ethylamino)-5-isopropyl-pyrimidin-2-ylamino]-benzoicacidl50 mg ofN-[2-(2-chloro-5-isopropyl-pyrimidin-4-ylamino)-ethyl]-acetamide,methyl-4-aminobenzoate (5 eq.) and 10 mg of 4-dimethylaminopyridine areheated to 150° C. in 2 ml of isopropanol in a sealed reaction vessel for48 hours. After extraction with ethyl acetate from saturated bicarbonatesolution the mixture is dried over sodium sulphate and evaporated down.Chromatography (CH₂Cl₂/MeOH gradient, silica gel) yields themethylester. This is taken up in 3 ml of methanol, combined with a 1 MLiOH solution (10 eq.) and treated at 50° C. for up to 24 hours. The pHis adjusted to 5 by adding a 10% NaH₂PO₄ solution (or alternatively topH=4 with a 1 M HCl solution) and the product is precipitated. Afterfiltration the product is washed with water, diethylether and ethylacetate and dried in vacuo. 95 mg of product are obtained.

[2798] Melting point: 275-278° C.

[2799] R_(f)=0,04 (silica gel; methylene chloride:methanol=4:1)

[2800] HPLC/MS (method G): RT=3,01 min.; [M+H]+=358; Abs. λ max=291,2 nm

[2801] The following compounds are obtained analogously to Example 6:

[2802] (1)4-(5-methanesulphonyl-4-[3-(2-oxo-pyrrolidin-1-yl)-propylamino]-pyrimidin-2-ylamino]-benzoicacid

[2803] Melting point: >270° C. decomposition

[2804] R_(f)=0.17 (silica gel; methylene chloride:methanol=9:1)

[2805] HPLC/MS (method F): RT=3,43 min.; [M+H]+=434; Abs. λ max=293 nm

[2806] (2)4-(5-methoxy-4-[3-(2-oxo-pyrrolidin-1-yl)-propylamino]-pyrimidin-2-ylamino]-benzoicacid

[2807] Melting point: >218° C. decomposition

[2808] R_(f)=0.12 (silica gel; methylene chloride:methanol=9:1)

[2809] HPLC/MS (method J): RT=4,88 min.; [M+H]+=386; Abs. λ max=298,8 nm

[2810] (3)4-(5-dimethylamino-4-[3-(2-oxo-pyrrolidin-1-yl)-propylamino]-pyrimidin-2-ylamino]-benzoicacid

[2811] Melting point: >235° C. decomposition

[2812] R_(f)=0.1 (silica gel; methylene chloride:methanol=9:1)

[2813] HPLC/MS (method G): RT=3,08 min.; [M+H]+=399; Abs. λ max=298,8 nm

[2814] (4)4-[4-(2-acetylamino-ethylamino)-5-trifluoromethyl-pyrimidin-2-ylamino]-2-chloro-benzoicacid

[2815] Melting point: 261° C.

[2816] R_(f)=0.15 (silica gel; methylene chloride:methanol=4:1)

[2817] HPLC/MS (method G): RT=3,28 min.; [M+H]+=418; Abs. λ max=251,3 nm

[2818] 1H-NMR(D₆-DMSO, 300 MHz) δ: 1.80 (s, 3H), 3.34 (m, 2H), 3.54 (m,2H), 7.54 (m, 1H), 7.78 (m, 1H), 7.84 (m, 1H), 8.03 (m, 2H), 8.30 (s,1H), 10.23 (s, 1H).

[2819] (5)4-[4-(2-acetylamino-ethylamino)-5-trifluoromethyl-pyrimidin-2-ylamino]-3-chloro-benzoicacid

[2820] Melting point: 245° C.

[2821] R_(f)=0,33 (silica gel; methylene chloride:methanol=4:1)

[2822] HPLC/MS (method G): RT=3,35 min.; [M+H]+=418; Abs. λ max=253,2 nm

[2823] 1H-NMR(D₆-DMSO, 300 MHz): 1.78 (s, 3H), 3.24 (m, 2H), 3.43 (m,2H), 7.31 (t, 1H), 7.90 (m, 3H), 8.20 (m, 2H), 8.76 (s, 1H), 13.04 (s,1H).

[2824] (6)4-[5-methoxy-4-(4-pyridin-2-yl-piperazin-1-yl)-pyrimidin-2-ylamino]-benzoicacid

[2825] Melting point: >260° C. decomposition

[2826] R_(f)=0,23 (silica gel; methylene chloride:methanol=9:1)

[2827] HPLC/MS (method G): RT=2,84 min.; [M+H]+=407; Abs. λ max=298,8 nm

[2828] (7)4-(5-isopropyl-4-[3-(2-oxo-pyrrolidin-1-yl)-propylamino]-pyrimidin-2-ylamino]-benzoicacid

[2829] Melting point: >315° C.

[2830] R_(f)=0,08 (silica gel; methylene chloride:methanol=9:1)

[2831] HPLC/MS (method G): RT=3,21 min.; [M+H]+=398; Abs. λ max=257 nm

EXAMPLE 7

[2832]N-(2-[2-(3,4-dichloro-phenylamino)-5-trifluoromethyl-pyrimidin-4-ylamino]-ethyl)-benzamide

[2833] 100 mg ofN4-(2-amino-ethyl)-N-2-(3,4-dichloro-phenyl)-5-trifluoromethyl-pyrimidine-2,4-diamineweredissolved in pyridine/CH₂Cl₂ (1 ml/l ml) and cooled to 0° C. and 1.1 eqof benzoic acid chloride were slowly added to 1 ml of CH₂Cl₂. Thereaction mixture was allowed to heat up to ambient temperature andstirred overnight. After the addition of 2 ml of saturated NaHCO₃solution the mixture was extracted with ethyl acetate, dried over Na₂SO₄and evaporated down. Then the residue was washed with ethyl acetate,diethylether and dichloromethane and chromatographed over silica gel(CH₂Cl₂, MeOH). A yield of 83 mg was obtained.

[2834] Melting point: 226-228° C.

[2835] R_(f)=0.57 (silica gel; methylene chloride:methanol=99:1)

[2836] HPLC/MS (method I): RT=4,04 min.; [M+H]+=471; Abs. λ max=266,5 nm

[2837] The following compounds are obtained analogously to Example 7:

[2838] (1)N-(2-[2-(3,4-dichloro-phenylamino)-5-trifluoromethyl-pyrimidin-4-ylamino]-ethyl)-methanesulphonamide

[2839] 100 mg ofN4-(2-amino-ethyl)-N-2-(3,4-dichloro-phenyl)-5-trifluoromethyl-pyrimidine-2,4-diaminewere dissolved with diisopropylethylamine (4 eq.) in THF (2 ml) and 1.1eq of methanesulphonic acid chloride were slowly added. The reactionmixture was stirred for 4 hours. After the addition of 2 ml ofsaturated. NaHCO₃ solution the mixture was extracted with ethyl acetate,dried over Na₂SO₄ and evaporated down. Then the residue was washed withethyl acetate, diethylether and dichloromethane and chromatographed oversilica gel (CH₂Cl₂, MeOH). A yield of 91 mg was obtained.

[2840] Melting point: 195-196° C.

[2841] R_(f)=0.50 (silica gel; methylene chloride:methanol=99:1)

[2842] HPLC/MS (method K): RT=2,44 min.; [M+H]+=445; Abs. λ max=266,5 nm

[2843] (2)N-{3-[2-(1-methyl-1H-indazol-6-ylamino)-5-trifluoromethyl-pyrimidin-4-ylamino]-propyl}-isobutyramide

[2844] Prepared from compound 1 (674)

[2845] Melting point: 268° C.

[2846] R_(f)=0,38 (silica gel; methylene chloride:methanol=95:5)

[2847] HPLC/MS (method D): RT=5,50 min.; [M+H]+=436; Abs. λ max=250 nm

[2848] (3)N-(2-[2-(3,4-dichloro-phenylamino)-5-trifluoromethyl-pyrimidin-4-ylamino]-ethyl)-dimethylamino-acetamide

[2849] 100 mg ofN4-(2-amino-ethyl)-N-2-(3,4-dichloro-phenyl)-5-trifluoromethyl-pyrimidine-2,4-diamine[1(80)] were dissolved with dimethylaminoacetic acid (1 eq.),diisopropylethylamine (2 eq.), HOBT (1.3 eq.) and HBTU (1.3 eq.) in DMF(2 ml) and stirred overnight at ambient temperature. After the additionof 2 ml of 2 M NaHCO₃ solution the mixture was extracted with ethylacetate, dried over Na₂SO₄ and evaporated down. Then the residue waschromatographed over silica gel (CH₂Cl₂, MeOH). A yield of 62 mg wasobtained.

[2850] Melting point: 165-167° C.

[2851] R_(f)=0.17 (silica gel; methylene chloride:methanol=99:1)

[2852] HPLC/MS (method H): RT=3,07 min.; [M+H]+=452; Abs. λ max=264,6 nm

[2853] (4)N-(2-[2-(3,4-dichloro-phenylamino)-5-trifluoromethyl-pyrimidin-4-ylamino]-ethyl)-isobutyramide

[2854] Prepared from compound 1 (80).

[2855] Melting point: 232-235° C.

[2856] R_(f)=0.55 (silica gel; methylene chloride:methanol=99:1)

[2857] HPLC/MS (method I): RT=2,74 min.; [M+H]+=437; Abs. λ max=266,5 nm

[2858] (5)N-(2-[2-(3,4-dichloro-phenylamino)-5-trifluoromethyl-pyrimidin-4-ylamino]-ethyl)-methoxy-acetamide

[2859] Prepared from compound 1 (80).

[2860] Melting point: 197-201° C.

[2861] R_(f)=0.45 (silica gel; methylene chloride:methanol=99:1)

[2862] HPLC/MS (method G): RT=3,27 min.; [M+H]+=439; Abs. λ max=266,5 nm

[2863] (6)N-{3-[2-(1-methyl-1H-indazol-6-ylamino)-5-trifluoromethyl-pyrimidin-4-ylamino]-propyl}-propionamide

[2864] Prepared from compound 1 (674).

[2865] Melting point: 261° C.

[2866] R_(f)=0.37 (silica gel; methylene chloride:methanol=95:5)

[2867] HPLC/MS (method D): RT=5,30 min.

[2868] (7)N-{3-[2-(1-methyl-1H-indazol-6-ylamino)-5-trifluoromethyl-pyrimidin-4-ylamino]-propyl}-methanesulphonamide

[2869] Prepared from compound 1 (674)

[2870] Melting point: 230° C.

[2871] R_(f)=0.20 (silica gel; methylene chloride:methanol=95:5)

[2872] HPLC/MS (method D): RT=5,20 min.; [M+H]+=444; Abs. λ max=250 nm

[2873] (8)N-(2-[2-(3,4-dichloro-phenylamino)-5-trifluoromethyl-pyrimidin-4-ylamino]-ethyl)-N-methyl-isobutyramide

[2874] Prepared from compound 1 (240).

[2875] Melting point: 138-140° C.

[2876] R_(f)=0.33 (silica gel; methylene chloride:methanol=99:1)

[2877] HPLC/MS (method G): RT=4,80 min.; [M+H]+=451; Abs. λ max=274.1 nm

[2878] (9)N-(2-[2-(3,4-dichloro-phenylamino)-5-trifluoromethyl-pyrimidin-4-ylamino]-ethyl)-N-methyl-acetamide

[2879] Prepared from compound 1 (240).

[2880] Melting point: 174-175° C.

[2881] R_(f)=0.14 (silica gel; methylene chloride:methanol=99:1)

[2882] HPLC/MS (method G): RT=4.19 min.; [M+H]+=423; Abs. λ max=266.5 nm

[2883] (10)N-(3-[2-(3,4-dichloro-phenylamino)-5-trifluoromethyl-pyrimidin-4-ylamino]-propyl)-acetamide

[2884] Prepared from compound 1 (35).

[2885] Melting point: 200-203° C.

[2886] R_(f)=0,32 (silica gel; methylene chloride:methanol=99:1)

[2887] HPLC/MS (method F): RT=4.19 min.; [M+H]+=423; Abs. λ max=266,5 nm

[2888] (11)N-(3-[2-(3,4-dichloro-phenylamino)-5-trifluoromethyl-pyrimidin-4-ylamino]-propyl)-2-methoxy-acetamide

[2889] Prepared from compound 1 (35).

[2890] Melting point: 160-162° C.

[2891] R_(f)=0.61 (silica gel; methylene chloride:methanol=99:1)

[2892] HPLC/MS (method G): RT=4,27 min.; [M+H]+=453; Abs. ? max=266,5 nm

[2893] (12)4-fluoro-N-{3-[2-(1-methyl-1H-indazol-6-ylamino)-5-trifluoromethyl-pyrimidin-4-ylamino]-propyl}-benzensulphonamide

[2894] Prepared from compound 1 (674).

[2895] Melting point: 256° C.

[2896] R_(f)=0.30 (silica gel; methylene chloride:methanol=95:5)

[2897] HPLC/MS (method D): RT=6.20 min.; [M+H]+=524; Abs. λ max=242 nm

[2898] (13)2-methoxy-N-{3-[2-(1-methyl-1H-indazol-6-ylamino)-5-trifluoromethyl-pyrimidin-4-ylamino]-propyl}-acetamide

[2899] Prepared from compound 1 (674)

[2900] Melting point: 241° C.

[2901] R_(f)=0,38 (silica gel; methylene chloride:methanol=95:5)

[2902] HPLC/MS (method D): RT=5,20 min.; [M+H]+=438; Abs. λ max=250 nm

[2903] (14)N-1-[2-(3,4-dichloro-phenylamino)-5-trifluoromethyl-pyrimidin-4-yl]-pyrrolidine-3-yl)-acetamide

[2904] Prepared from compound 1 (338).

[2905] Melting point: 244-245° C.

[2906] R_(f)=0.11 (silica gel; methylene chloride:methanol=99:1)

[2907] HPLC/MS (method F): RT=4,37 min.; [M+H]+=435; Abs. λ max=268,4 nm

[2908] (15)3-methyl-N-{3-[2-(1-methyl-1H-indazol-6-ylamino)-5-trifluoromethyl-pyrimidin-4-ylamino]-propyl}-butyramide

[2909] Prepared from compound 1 (674)

[2910] Melting point: 254° C.

[2911] R_(f)=0.40 (silica gel; methylene chloride:methanol=95:5)

[2912] HPLC/MS (method D): RT=5,70 min.; [M+H]+=450; Abs. λ max=250 nm

[2913] (16)2-fluoro-N-{3-[2-(1-methyl-1H-indazol-6-ylamino)-5-trifluoromethyl-pyrimidin-4-ylamino]-propyl}-benzensulphonamide

[2914] Prepared from compound 1 (674)

[2915] Melting point: 253° C.

[2916] R_(f)=0,32 (silica gel; methylene chloride:methanol=95:5)

[2917] HPLC/MS (method D): RT=6,10 min.; [M+H]+=524; Abs. λ max=250 nm

[2918] (17)4-[4-(2-acetyl-methyl-amino)-ethylamino)-5-trifluoromethyl-pyrimidin-2-ylamino]-benzamide

[2919] Prepared from compound 1 (650).

[2920] Melting point: 250-252° C.

[2921] R_(f)=0.14 (silica gel; methylene chloride:methanol=9:1)

[2922] HPLC/MS (method G): RT=2,76 min.; [M+H]+=397; Abs. λ max=277,9 nm

[2923] (18)4-{4-[2-(2-dimethylamino-acetylamino)-ethylamino]-5-trifluoromethyl-pyrimidin-2-ylamino}-benzamide

[2924] Prepared from compound 1 (259)

[2925] Melting point: 215-218° C.

[2926] R_(f)=0,24 (silica gel; methylene chloride:methanol=4:1)

[2927] HPLC/MS (method F): RT=2,86 min.; [M+H]+=426; Abs. λ max=279,8 nm

[2928] (19)4-[4-(2-isobutyrylamino-ethylamino)-5-trifluoromethyl-pyrimidin-2-ylamino]-benzamide

[2929] Prepared from compound 1 (259).

[2930] Melting point: 247-250° C.

[2931] R_(f)=0.16 (silica gel; methylene chloride:methanol=9:1)

[2932] HPLC/MS (method F): RT=3,18 min.; [M+H]+=411; Abs. λ max=279,8 nm

[2933] (20)4-[4-(2-methanesulphonylamino-ethylamino)-5-trifluoromethyl-pyrimidin-2-ylamino]-benzamidePrepared from compound 1 (259).

[2934] Melting point: 255-256° C.

[2935] R_(f)=0.13 (silica gel; methylene chloride:methanol=9:1)

[2936] HPLC/MS (method G): RT=2,83 min.; [M+H]+=419; Abs. λ max=279,8 nm

[2937] (21)N-{3-[2-(1-methyl-1H-indazol-6-ylamino)-5-trifluoromethyl-pyrimidin-4-ylamino]-propyl}-2-phenyl-acetamide

[2938] Prepared from compound 1 (674).

[2939] Melting point: 230° C.

[2940] R_(f)=0.46 (silica gel; methylene chloride:methanol=95:5)

[2941] HPLC/MS (method D): RT=5,90 min.; [M+H]+=484; Abs. λ max=250 nm

[2942] (22){3-[2-(1-methyl-1H-indazol-6-ylamino)-5-trifluoromethyl-pyrimidin-4-ylamino]-propyl}-methylcarbamate

[2943] Prepared from compound 1 (674).

[2944] Melting point: 136° C.

[2945] R_(f)=0.46 (silica gel; methylene chloride:methanol=95:5)

[2946] HPLC/MS (method D): RT=5,50 min.; [M+H]+=424; Abs. λ max=250 nm

[2947] (23)4-(4-[2-(isobutyryl-methyl-amino)-ethylamino)-5-trifluoromethyl-pyrimidin-2-ylamino)-benzamide

[2948] Prepared from compound 1 (650).

[2949] Melting point: 250-253° C.

[2950] R_(f)=0.19 (silica gel; methylene chloride:methanol=9:1)

[2951] HPLC/MS (method G): RT=3,12 min.; [M+H]+=424; Abs. λ max=279,8 nm

[2952] (24){3-[2-(1-methyl-1H-indazol-6-ylamino)-5-trifluoromethyl-pyrimidin-4-ylamino]-propyl}-isobutylcarbamate

[2953] Prepared from compound 1 (674).

[2954] Melting point: 226° C.

[2955] R_(f)=0.50 (silica gel; methylene chloride:methanol=95:5)

[2956] HPLC/MS (method C): RT=4,40 min.; [M+H]+=466; Abs. λ max=250 nm

[2957] (25){3-[2-(1-methyl-1H-indazol-6-ylamino)-5-trifluoromethyl-pyrimidin-4-ylamino]-propyl}-2-chlorobenzylcarbamate

[2958] Prepared from compound 1 (674)

[2959] Melting point: 194° C.

[2960] R_(f)=0,60 (silica gel; methylene chloride:methanol=95:5)

[2961] HPLC/MS (method D): RT=6,60 min.; [M+H]+=536; Abs. λ max=254 nm

[2962] (26)N-(3-[2-(3,4-dichloro-phenylamino)-5-trifluoromethyl-pyrimidin-4-ylamino]-propyl)-2-dimethylamino-acetamide

[2963] Prepared from compound 1 (35).

[2964] Melting point: 187-189° C.

[2965] R_(f)=0,09 (silica gel; methylene chloride:methanol=99:1)

[2966] HPLC/MS (method G): RT=3,85 min.; [M+H]+=466; Abs. λ max=268,4 nm

[2967] (27)4-[4-(3-acetylamino-propylamino)-5-trifluoromethyl-pyrimidin-2-ylamino]-benzamide

[2968] Prepared from compound 1 (697).

[2969] Melting point: 212-213° C.

[2970] R_(f)=0.13 (silica gel; methylene chloride:methanol=9:1)

[2971] HPLC/MS (method F): RT=3,01 min.; [M+H]+=397; Abs. λ max=279,8 nm

[2972] (28)4-[4-(3-(2-methoxy-acetamino)-propylamino)-5-trifluoromethyl-pyrimidin-2-ylamino]-benzamide

[2973] Prepared from compound 1 (697).

[2974] Melting point: 212-213° C.

[2975] R_(f)=0,09 (silica gel; methylene chloride:methanol=99:1)

[2976] HPLC/MS (method F): RT=3,12 min.; [M+H]+=467; Abs. λ max=279,8 nm

[2977] (29)4-(4-[3-(2-dimethylamino-acetylamino)-propylamino]-5-trifluoromethyl-pyrimidin-2-ylamino)-benzamide

[2978] Prepared from compound 1 (697).

[2979] Melting point: 184-187° C.

[2980] R_(f)=0.10 (silica gel; methylene chloride:methanol=9:1)

[2981] HPLC/MS (method F): RT=2,90 min.; [M+H]+=440; Abs. λ max=279,8 nm

[2982] (30)N-{3-[2-(1-methyl-1H-indazol-6-ylamino)-5-trifluoromethyl-pyrimidin-4-ylamino]-propyl}-benzensulphonamide

[2983] Prepared from compound 1 (674).

[2984] Melting point: 264° C.

[2985] R_(f)=0,28 (silica gel; methylene chloride:methanol=95:5)

[2986] HPLC/MS (method D): RT=6,10 min.; [M+H]+=506; Abs. λ max=238 m

[2987] (31)4-[4-{3-acetylamino-pyrrolidin-1-yl)-5-trifluoromethyl-pyrimidin-2-ylamino)-benzamide

[2988] Prepared from compound 1 (459).

[2989] Melting point: 244-246° C.

[2990] R_(f)=0.1 (silica gel; methylene chloride:methanol=9:1)

[2991] HPLC/MS (method G): RT=2,90 min.; [M+H]+=409; Abs. λ max=283,6 nm

[2992](32)1,1-diethyl-3-{3-[2-(1-methyl-1H-indazol-6-ylamino)-5-trifluoromethyl-pyrimidin-4-ylamino]-propyl}-urea

[2993] Prepared from compound 1 (674).

[2994] Melting point: 228° C.

[2995] R_(f)=0,36 (silica gel; methylene chloride:methanol=95:5)

[2996] HPLC/MS (method D): RT=5,70 min.; [M+H]+=465; Abs. λ max=250 nm

[2997] (33)4-[4-(2-benzoylamino-ethylamino)-5-trifluoromethyl-pyrimidin-2-ylamino]-benzamide

[2998] Prepared from compound 1 (259)

[2999] Melting point: 238-240° C.

[3000] R_(f)=0,26 (silica gel; methylene chloride:methanol=9:1)

[3001] HPLC/MS (method G): RT=3,22 min.; [M+H]+=445; Abs. λ max=279,8 nm

[3002] (34)4-(4-[2-(2-methoxy-acetylamino)-ethylamino]-5-trifluoromethyl-pyrimidin-2-ylamino]-benzamide

[3003] Prepared from compound 1 (259)

[3004] Melting point: 232-234° C.

[3005] R_(f)=0,29 (silica gel; methylene chloride:methanol=9:1)

[3006] HPLC/MS (method G): RT=2,77 min.; [M+H]+=413; Abs. λ max=279,8 nm

[3007](35)1,1-dimethyl-3-{3-[2-(1-methyl-1H-indazol-6-ylamino)-5-trifluoromethyl-pyrimidin-4-ylamino]-propyl}-urea

[3008] Prepared from compound 1 (674)

[3009] Melting point: 259° C.

[3010] R_(f)=0.59 (silica gel; methylene chloride:methanol=95:5)

[3011] HPLC/MS (method D): RT=5,20 min.; [M+H]+=437; Abs. λ max 250 nm

[3012](36)1-isopropyl-3-{3-[2-(1-methyl-1H-indazol-6-ylamino)-5-trifluoromethyl-pyrimidin-4-ylamino]-propyl}-urea

[3013] Prepared from compound 1 (674)

[3014] Melting point: 190° C.

[3015] R_(f)=0,08 (silica gel; methylene chloride:methanol=98:2)

EXAMPLE 8

[3016]4-[4-(2-acetylamino-ethylamino)-5-trifluoromethyl-pyrimidin-2-ylamino]-N-methyl-benzamide

[3017] 100 mg of4-[4-(2-acetylamino-ethylamino)-5-trifluoromethyl-pyrimidin-2-ylamino]-benzoicacid 9(1), methylamine (1.3 eq.), HOBT (1.3 eq.), HBTU (1.3 eq.) anddiisopropylethylamine (3 eq.) are added to 2 ml of DMF and stirredovernight. The reaction mixture is combined with saturated bicarbonatesolution and extracted with ethyl acetate. Then the organic phase iswashed with water, dried over sodium sulphate and evaporated down. Thecrude product is washed with ethyl acetate, diethylether anddichloromethane and optionally purified by chromatography (silica gel,CH₂Cl₂/MeOH gradient). A yield of 39 mg is obtained.

[3018] Melting point: 196° C.

[3019] R_(f)=0.11 (silica gel; methylene chloride:methanol=95:5) Rt(HPLC, method F)=3,06 min; [M+H]+=397; Abs. λ max=279,8 nm

[3020] The following compounds are obtained analogously to Example 8:

[3021] (1)3-[4-(2-acetylamino-ethylamino)-5-trifluoromethyl-pyrimidin-2-ylamino]-N-methyl-benzamide

[3022] Prepared from compound 9 (0).

[3023] Melting point: 291° C.

[3024] R_(f)=0.12 (silica gel; methylene chloride:methanol=9:1)

[3025] HPLC/MS (method G): RT=2,88 min.; [M+H]+397; Abs. λ max 239,9 nm

[3026] (2)4-[4-(2-acetylamino-ethylamino)-5-trifluoromethyl-pyrimidin-2-ylamino]-3-chloro-N-methyl-benzamide

[3027] Prepared from compound 6 (5)

[3028] Melting point: 252° C.

[3029] R_(f)=0,09 (silica gel; methylene chloride:methanol=9:1)

[3030] HPLC/MS (method G): RT=3,04 min.; [M+H]+=431; Abs. λ max=251,3 nm

[3031] (3)4-[4-(2-acetylamino-ethylamino)-5-trifluoromethyl-pyrimidin-2-ylamino]-2-chloro-N-methyl-benzamide

[3032] Prepared from compound 6 (4)

[3033] Melting point: 183° C.

[3034] R_(f)=0.10 (silica gel; methylene chloride:methanol=9:1)

[3035] HPLC/MS (method G): RT=2,89 min.; [M+H]+=431; Abs. λ max=270,3 nm

[3036] (4)4-[4-(2-acetylamino-ethylamino)-5-trifluoromethyl-pyrimidin-2-ylamino]-N,N-dimethyl-benzamide

[3037] Prepared from compound 9 (1).

[3038] Melting point: 185° C.

[3039] R_(f)=0.14 (silica gel; methylene chloride:methanol=9:1)

[3040] HPLC/MS (method G): RT=2,84 min.; [M+H]+=411; Abs. λ max=262,7 nm

[3041] (5)3-[4-(2-acetylamino-ethylamino)-5-trifluoromethyl-pyrimidin-2-ylamino]-N,N-dimethyl-benzamide

[3042] Prepared from compound 9 (0).

[3043] Melting point: 205° C.

[3044] R_(f)=0.19 (silica gel; methylene chloride:methanol=9:1)

[3045] HPLC/MS (method G): RT=2,88 min.; [M+H]+=411; Abs. λ max=245,6 nm

[3046] (6)4-[4-(2-acetylamino-ethylamino)-5-trifluoromethyl-pyrimidin-2-ylamino]-3-chloro-N,N-dimethyl-benzamide

[3047] Prepared from compound 6 (5).

[3048] Melting point: 135° C.

[3049] R_(f)=0.54 (silica gel; methylene chloride:methanol=9:1)

[3050] HPLC/MS (method G): RT=3,01 min.; [M+H]+=445; Abs. λ max=219 nm

[3051] (7)4-[4-(2-acetylamino-ethylamino)-5-trifluoromethyl-pyrimidin-2-ylamino]-2-chloro-N,N-dimethyl-benzamide

[3052] Prepared from compound 6 (4).

[3053] Melting point: 198° C.

[3054] R_(f)=0.14 (silica gel; methylene chloride:methanol=9:1)

[3055] HPLC/MS (method G): RT=3,09 min.; [M+H]+=445; Abs. λ max=253 nm

[3056] (8)4-[4-(2-acetylamino-ethylamino)-5-trifluoromethyl-pyrimidin-2-ylamino]-N-benzyl-N-methyl-benzamide

[3057] Prepared from compound 9 (1).

[3058] Melting point: 214° C.

[3059] R_(f)=0.18 (silica gel; methylene chloride:methanol=9:1)

[3060] HPLC/MS (method G): RT=3,52 min.; [M+H]+=487; Abs. λ max=253,2 nm

[3061] (9)3-[4-(2-acetylamino-ethylamino)-5-trifluoromethyl-pyrimidin-2-ylamino]-N-benzyl-N-methyl-benzamide

[3062] Prepared from compound 9 (0).

[3063] Melting point: 157° C.

[3064] R_(f)=0,24 (silica gel; methylene chloride:methanol=9:1)

[3065] HPLC/MS (method G): RT=3,59 min.; [M+H]+=487; Abs. λ max=203,8 nm

[3066] (10)4-[4-(2-acetylamino-ethylamino)-5-trifluoromethyl-pyrimidin-2-ylamino]-3-chloro-N-benzyl-N-methyl-benzamide

[3067] Prepared from compound 6 (5).

[3068] Melting point: 152° C.

[3069] R_(f)=0,22 (silica gel; methylene chloride:methanol=9:1)

[3070] HPLC/MS (method G): RT=3,78 min.; [M+H]+=521; Abs. λ max=209,5 nm

[3071] (11)4-[4-(2-acetylamino-ethylamino)-5-trifluoromethyl-pyrimidin-2-ylamino]-2-chloro-N-benzyl-N-methyl-benzamide

[3072] Prepared from compound 6 (4).

[3073] Melting point: 180° C.

[3074] R_(f)=0,20 (silica gel; methylene chloride:methanol=9:1)

[3075] HPLC/MS (method G): RT=3,85 min.; [M+H]+=522; Abs. λ max=268,4 nm

[3076] (12)N-(2-(2-[4-(piperidin-1-carbonyl)-phenylamino]-5-trifluoromethyl-pyrimidin-4-ylamino)-ethyl)-acetamide

[3077] Prepared from compound 9 (1).

[3078] Melting point: 199° C.

[3079] R_(f)=0,67 (silica gel; methylene chloride:methanol=85:15)

[3080] HPLC/MS (method G): RT=3,25 min.; [M+H]+=451; Abs. λ max=266,5 nm

[3081] (13)N-(2-(2-[3-(piperidin-1-carbonyl)-phenylamino]-5-trifluoromethyl-pyrimidin-4-ylamino)-ethyl)-acetamide

[3082] Prepared from compound 9 (O).

[3083] Melting point: 179° C.

[3084] R_(f)=0,21 (silica gel; methylene chloride:methanol=9:1)

[3085] HPLC/MS (method G): RT=3,30 min.; [M+H]+=451; Abs. λ max=245,6 nm

[3086] (14)N-(2-(2-[2-Chloro-4-(piperidin-1-carbonyl)-phenylamino]-5-trifluoromethyl-pyrimidin-4-ylamino)-ethyl)-acetamide

[3087] Prepared from compound 6 (5).

[3088] Melting point: 108° C.

[3089] R_(f)=0,22 (silica gel; methylene chloride:methanol=9:1)

[3090] HPLC/MS (method G): RT=3,44 min.; [M+H]+=485; Abs. λ max=243,7 nm

[3091] (15)N-(2-(2-[3-Chloro-4-(piperidin-1-carbonyl)-phenylamino]-5-trifluoromethyl-pyrimidin-4-ylamino)-ethyl)-acetamide

[3092] Prepared from compound 6 (4).

[3093] Melting point: 193° C.

[3094] R_(f)=0,22 (silica gel; methylene chloride:methanol=9:1)

[3095] HPLC/MS (method G): RT=3,52 min.; [M+H]+=485; Abs. λ max=266,5 nm

[3096] (16)N-(2-(2-[4-(Morpholin-4-carbonyl)-phenylamino]-5-trifluoromethyl-pyrimidin-4-ylamino)-ethyl)-acetamide

[3097] Prepared from compound 9 (1).

[3098] Melting point: 221° C.

[3099] R_(f)=0,65 (silica gel; methylene chloride:methanol=85:15)

[3100] HPLC/MS (method G): RT=2,85 min.; [M+H]+=453; Abs. λ max=262,7 nm

[3101] (17)N-(2-(2-[3-(Morpholin-4-carbonyl)-phenylamino]-5-trifluoromethyl-pyrimidin-4-ylamino)-ethyl)-acetamide

[3102] Prepared from compound 9 (0).

[3103] Melting point: 196° C.

[3104] R_(f)=0.18 (silica gel; methylene chloride:methanol=9:1)

[3105] HPLC/MS (method G): RT=2,89 min.; [M+H]+=453; Abs. λ max=245,6 nm

[3106] (18)N-(2-(2-[2-Chloro-4-(morpholine-4-carbonyl)-phenylamino]-5-trifluoromethyl-pyrimidin-4-ylamino)-ethyl)-acetamide

[3107] Prepared from compound 6 (5).

[3108] Melting point: 40° C.

[3109] R_(f)=0,20 (silica gel; methylene chloride:methanol=9:1)

[3110] HPLC/MS (method G): RT=3,31 min.; [M+H]+=487; Abs. λ max=220,9 nm

[3111] (19)N-(2-(2-[3-Chloro-4-(morpholine-4-carbonyl)-phenylamino]-5-trifluoromethyl-pyrimidin-4-ylamino)-ethyl)-acetamide

[3112] Prepared from compound 6 (4).

[3113] Melting point: 197° C.

[3114] R_(f)=0,20 (silica gel; methylene chloride:methanol=9:1)

[3115] HPLC/MS (method G): RT=3,09 min.; [M+H]+=487; Abs. λ max=266,5 nm

[3116] (20)N-(2-{2-[4-(4-methyl-piperazin-1-carbonyl)-phenylamino]-5-trifluoromethyl-pyrimidin-4-ylamino}-ethyl)-acetamide

[3117] Prepared from compound 9 (1).

[3118] Melting point: 228° C.

[3119] R_(f)=0,37 (silica gel; methylene chloride:methanol=85:15)

[3120] HPLC/MS (method G): RT=2,39 min.; [M+H]+=466; Abs. λ max=272,2 nm

[3121] (21)N-(2-(2-[3-(4-methyl-piperazin-1-carbonyl)-phenylamino]-5-trifluoromethyl-pyrimidin-4-ylamino)-ethyl)-acetamide

[3122] Prepared from compound 9 (0).

[3123] Melting point: 186° C.

[3124] R_(f)=0.54 (silica gel; methylene chloride:methanol=4:1)

[3125] HPLC/MS (method G): RT=2,50 min.; [M+H]+=466; Abs. λ max=245,6 nm

[3126] (22)4-[4-(2-acetylamino-ethylamino)-5-trifluoromethyl-pyrimidin-2-ylamino]-N-pyridin-2-ylmethyl-benzamide

[3127] Prepared from compound 9 (1).

[3128] Melting point: 229° C.

[3129] R_(f)=0,61 (silica gel; methylene chloride:methanol=85:15)

[3130] HPLC/MS (method G): RT=2,68 min.; [M+H]+=474; Abs. λ max=281,7 nm

[3131] (23)3-[4-(2-acetylamino-ethylamino)-5-trifluoromethyl-pyrimidin-2-ylamino]-N-pyridin-2-ylmethyl-benzamide

[3132] Prepared from compound 9 (0).

[3133] Melting point: 216° C.

[3134] R_(f)=0,69 (silica gel; methylene chloride:methanol=85:15)

[3135] HPLC/MS (method G): RT=2,70 min.; [M+H]+=474; Abs. λ max=260,8 nm

[3136] (24)4-[4-(2-acetylamino-ethylamino)-5-trifluoromethyl-pyrimidin-2-ylamino]-N-pyridin-2-yl-benzamide

[3137] Prepared from compound 9 (1).

[3138] Melting point: 225° C.

[3139] R_(f)=0,09 (silica gel; methylene chloride:methanol=85:15)

[3140] HPLC/MS (method G): RT=4,24 min.; [M+H]+=460; Abs. λ max=205,7 nm

[3141] (25)3-[4-(2-acetylamino-ethylamino)-5-trifluoromethyl-pyrimidin-2-ylamino]-N-pyridin-2-yl-benzamide

[3142] Prepared from compound 9 (0).

[3143] Melting point: 251° C.

[3144] R_(f)=0,20 (silica gel; methylene chloride:methanol=9:1)

[3145] HPLC/MS (method G): RT=2,99 min.; [M+H]+=460; Abs. λ max=247,5 nm

[3146] (26)4-[4-(2-acetylamino-ethylamino)-5-trifluoromethyl-pyrimidin-2-ylamino]-N-(3,5-difluorobenzyl)-benzamide

[3147] Prepared from compound 9 (1).

[3148] Melting point: 231° C.

[3149] R_(f)=0.11 (silica gel; methylene chloride:methanol=9:1)

[3150] HPLC/MS (method G): RT=3,67 min.; [M+H]+=509; Abs. λ max=281,7 nm

[3151] (27)3-[4-(2-acetylamino-ethylamino)-5-trifluoromethyl-pyrimidin-2-ylamino]-N-(3,5-difluorobenzyl)-benzamide

[3152] Prepared from compound 9 (0).

[3153] Melting point: 226° C.

[3154] R_(f)=0,72 (silica gel; methylene chloride:methanol=85:15)

[3155] HPLC/MS (method G): RT=3,71 min.; [M+H]+=509; Abs. λ max=239,9 nm

[3156] (28)4-[4-(2-acetylamino-ethylamino)-5-trifluoromethyl-pyrimidin-2-ylamino]-N-(1-phenyl-ethyl)-benzamide

[3157] Prepared from compound 9 (1).

[3158] Melting point: 237° C.

[3159] R_(f)=0.10 (silica gel; methylene chloride:methanol=9:1)

[3160] HPLC/MS (method G): RT=3,60 min.; [M+H]+=487; Abs. λ max=279,8 nm

[3161] (29)3-[4-(2-acetylamino-ethylamino)-5-trifluoromethyl-pyrimidin-2-ylamino]-N-(1-phenyl-ethyl)-benzamide

[3162] Prepared from compound 9 (0).

[3163] Melting point: 234° C.

[3164] R_(f)=0,23 (silica gel; methylene chloride:methanol=9:1)

[3165] HPLC/MS (method G): RT=3,66 min.; [M+H]+=487; Abs. λ max=241,8 nm

EXAMPLE 9

[3166]3-[4-(2-acetylamino-ethylamino)-5-trifluoromethyl-pyrimidin-2-ylamino]-benzoicacidN-[2-(2-Chloro-5-trifluoromethyl-pyrimidin-4-ylamino)-ethyl]-acetamide(1 eq.), 3-aminobenzoic acid (4 eq.) and isopropanol are heatedovernight at 60° C. The reaction mixture is diluted with ethyl acetateand washed with 0.01 N HCL solution. The solid formed is filtered offand washed with ethyl acetate by centrifugation and if necessarypurified by chromatography (silica gel CH₂Cl₂/MeOH/AcOH=10:1:0.1). Awhite solid is obtained in an 89% yield.

[3167] Melting point: 282° C.

[3168] R_(f)=0.33 (silica gel; methylene chloride:methanol=4:1)

[3169] HPLC/MS (method G): RT=3,02 min.; [M+H]+=384; Abs. λ max=238 nm

[3170] 1H-NMR(D₆-DMSO, 300 MHz) δ: 1.81 (s, 3H), 3.32 (m, 2H), 3.55 (m,2H), 7.22 (m, 1H), 7.42 (m, 1H), 7.56 (m, 1H), 7.90 (m, 2H), 8.22 (s,1H), 8.52 (s, 1H), 8.85 (s, 1H).

[3171] The following compound was obtained analogously to Example 9:

[3172] (1)4-[4-(2-acetylamino-ethylamino)-5-trifluoromethyl-pyrimidin-2-ylamino]-benzoicacid Melting point: 260° C.

[3173] R_(f)=0.33 (silica gel; methylenechloride:methanol:conc.ammonia=4:1:0.25)

[3174] Rt (HPLC, method E)=3.21 min.

[3175] 1H-NMR(D₆-DMSO, 300 MHz) δ: 1.82 (s, 3H), 3.33 (m, 2H), 3.54 (m,2H), 7.29 (m, 1H), 7.88 (m, 5H), 8.00 (m, 1H), 8.25 (s, 1H), 10.00 (s,1H).

EXAMPLE 10

[3176]N-(2-[2-(3-acetylamino-phenylamino)-5-trifluoromethyl-pyrimidin-4-ylamino]-ethyl)-acetamide

[3177] 100 mg ofN-(2-[2-(3-amino-phenylamino)-5-trifluoromethyl-pyrimidin-4-ylamino]-ethyl)-acetamide[2(67)] in 1 ml of pyridine and 1 ml dichloromethane are mixed at 0° C.with acetylchloride (1.1 eq.) in 0.5 ml of dichloromethane, heated toambient temperature and stirred overnight. The reaction mixture is mixedwith 2 ml saturated bicarbonate solution and extracted with ethylacetate. The organic phases are dried over sodium sulphate andevaporated down. The crude product is washed with ethyl acetate,diethylether and dichloromethane and optionally purified bychromatography (silica gel, CH₂Cl₂/MeOH gradient). 102 mg of a solid areobtained.

[3178] Melting point: 220° C.

[3179] R_(f)=0.11 (silica gel; methylene chloride:methanol=9:1)

[3180] HPLC/MS (method F): RT=3,12 min.; [M+H]+=397; Abs. λ max=245,6 nm

[3181] (1) pyridine-2-carboxylic acid(3-[4-(2-acetylamino-ethylamino)-5-trifluoromethyl-pyrimidin-2-ylamino]-phenyl)-amide

[3182] 100 mg ofN-(2-[2-(3-amino-phenylamino)-5-trifluoromethyl-pyrimidin-4-ylamino]-ethyl)-acetamide[2(67)] are stirred overnight at ambient temperature with2-pyridinecarboxylic acid (1.2 eq.), HOBT (1.2 eq.), HBTU (1.2 eq.) anddiisopropylethylamine (2 eq.) in 2 ml of DMF. The reaction mixture iscombined with 2 ml of saturated bicarbonate solution and extracted withethyl acetate. The organic phases are dried over sodium sulphate andevaporated down. The crude product is washed with ethyl acetate,diethylether and dichloromethane and optionally purified bychromatography (silica gel, CH₂Cl₂/MeOH gradient). 109 mg of a solid areobtained.

[3183] Melting point: 184° C.

[3184] R_(f)=0.24 (silica gel; methylene chloride:methanol=9:1)

[3185] HPLC/MS (method F): RT=3,69 min.; [M+H]+=460; Abs. λ max=262,7 nm

[3186] The following compounds are obtained analogously to Example 10 or10 (1):

[3187] (2)N-14-[4-(2-acetylamino-ethylamino)-5-trifluoromethyl-pyrimidin-2-ylamino]-phenyl}-3,5-difluoro-N-methyl-benzamide

[3188] Prepared from compound 2 (130).

[3189] Melting point: 103-106° C.

[3190] R_(f)=0.45 (silica gel; methylene chloride:methanol=9:1)

[3191] HPLC/MS (method F): RT=3.83 min.; [M+H]+=509; Abs. λ max=261 nm

[3192] (3)N-(2-[2-(4-acetylamino-phenylamino)-5-trifluoromethyl-pyrimidin-4-ylamino]-ethyl)-acetamide

[3193] Prepared from compound 2 (4)

[3194] Melting point: 222° C.

[3195] R_(f)=0,65 (silica gel; methylene chloride:methanol=4:1)

[3196] HPLC/MS (method F): RT=3,05 min.; [M+H]+=397; Abs. λ max=266,5 nm

[3197] (4)N-(3-[4-(2-acetylamino-ethylamino)-5-trifluoromethyl-pyrimidin-2-ylamino]-phenyl)-benzamide

[3198] Prepared from compound 2 (67).

[3199] Melting point: 215° C.

[3200] R_(f)=0,29 (silica gel; methylene chloride:methanol=9:1)

[3201] HPLC/MS (method F): RT=3,67 min.; [M+H]+=459; Abs. λ max=257 nm

[3202] (5)N-(4-[4-(2-acetylamino-ethylamino)-5-trifluoromethyl-pyrimidin-2-ylamino]-phenyl)-benzamide

[3203] Prepared from compound 2 (4)

[3204] Melting point: 252° C.

[3205] R_(f)=0.17 (silica gel; methylene chloride:methanol=9:1)

[3206] HPLC/MS (method F): RT=3,59 min.; [M+H]+=459; Abs. λ max=219 nm

[3207] (6) pyridine-2-carboxylic acid(4-[4-(2-acetylamino-ethylamino)-5-trifluoromethyl-pyrimidin-2-ylamino]-phenyl)-amide

[3208] Prepared from compound 2 (4).

[3209] Melting point: 215° C.

[3210] R_(f)=0,22 (silica gel; methylene chloride:methanol=9:1)

[3211] HPLC/MS (method F): RT=3,61 min.; [M+H]+=460; Abs. λ max=220,9 nm

[3212] (7) pyridine-2-carboxylic acid{4-[4-(2-acetylamino-ethylamino)-5-trifluoromethyl-pyrimidin-2-ylamino]-phenyl}-methyl-amide

[3213] Prepared from compound 2 (130).

[3214] Melting point: 144-145° C.

[3215] R_(f)=0.43 (silica gel; methylene chloride:methanol=9:1)

[3216] HPLC/MS (method F): RT=3,32 min.; [M+H]+=474; Abs. λ max=263 nm

[3217] (8)N-(2-{2-[4-(phenylsulphonyl-methyl-amino)-phenylamino]-5-trifluoromethyl-pyrimidin-4-ylamino}-ethyl)-acetamide

[3218] Prepared from compound 2 (130).

[3219] Melting point: 162-164° C.

[3220] R_(f)=0.56 (silica gel; methylene chloride:methanol=9:1)

[3221] HPLC/MS (method F): RT=3,99 min.; [M+H]+=509; Abs. λ max=267 nm

[3222] (9)N-{3-[4-(2-acetylamino-ethylamino)-5-trifluoromethyl-pyrimidin-2-ylamino]-phenyl}-3,5-difluoro-N-methyl-benzamide

[3223] Prepared from compound 2 (131).

[3224] Melting point: 193-195° C.

[3225] R_(f)=0.43 (silica gel; methylene chloride:methanol=9:1)

[3226] HPLC/MS (method H): RT=3,31 min.; [M+H]+=509; Abs. λ max=253 nm

[3227] (10) pyridine-2-carboxylic acid{3-[4-(2-acetylamino-ethylamino)-5-trifluoromethyl-pyrimidin-2-ylamino]-phenyl}-methyl-amide

[3228] Prepared from compound 2 (131).

[3229] Melting point: 188-190° C.

[3230] R_(f)=0.49 (silica gel; methylene chloride:methanol=9:1)

[3231] HPLC/MS (method G): RT=3,16 min.; [M+H]+=474; Abs. % max=253 nm

[3232] (11)N-(2-{2-[3-(phenylsulphonyl-methyl-amino)-phenylamino]-5-trifluoromethyl-pyrimidin-4-ylamino}-ethyl)-acetamide

[3233] Prepared from compound 2 (131).

[3234] Melting point: 117-120° C.

[3235] R_(f)=0,62 (silica gel; methylene chloride:methanol=9:1)

[3236] HPLC/MS (method F): RT=3,97 min.; [M+H]+=; 509 Abs. λ max=234 nm

[3237] (12)N-(4-[4-(2-acetylamino-ethylamino)-5-trifluoromethyl-pyrimidin-2-ylamino]-phenyl)-3,5-difluoro-benzamide

[3238] Prepared from compound 2 (4).

[3239] Melting point: 277° C.

[3240] R_(f)=0.18 (silica gel; methylene chloride:methanol=9:1)

[3241] HPLC/MS (method G): RT=3,74 min.; [M+H]+=495; Abs. λ max=219 nm

[3242] (13)N-(2-[2-(3-methanesulphonylamido-phenylamino)-5-trifluoromethyl-pyrimidin-4-ylamino]-ethyl)-acetamide

[3243] Prepared from compound 2 (67).

[3244] Melting point: 188° C.

[3245] R_(f)=0.15 (silica gel; methylene chloride:methanol=9:1)

[3246] HPLC/MS (method F): RT=3,22 min.; [M+H]+=433; Abs. λ max=243,7 nm

[3247] (14)N-(2-[2-(4-methanesulphonylamido-phenylamino)-5-trifluoromethyl-pyrimidin-4-ylamino]-ethyl)-acetamide

[3248] Prepared from compound 2 (4).

[3249] Melting point: 237° C.

[3250] R_(f)=0.17 (silica gel; methylene chloride:methanol=9:1)

[3251] HPLC/MS (method F): RT=3,14 min.; [M+H]+=433; Abs. λ max=263 nm

[3252] (15)N-(2-[2-(3-phenylsulphonylamido-phenylamino)-5-trifluoromethyl-pyrimidin-4-ylamino]-ethyl)-acetamide

[3253] Prepared from compound 2 (67).

[3254] Melting point: 208° C.

[3255] R_(f)=0,20 (silica gel; methylene chloride:methanol=9:1)

[3256] HPLC/MS (method F): RT=3,75 min.; [M+H]+=495; Abs. λ max=236.1 nm

[3257] (16)N-(2-[2-(4-phenylsulphonylamido-phenylamino)-5-trifluoromethyl-pyrimidin-4-ylamino]-ethyl)-acetamide

[3258] Prepared from compound 2 (4).

[3259] Melting point: 242° C.

[3260] R_(f)=0,22 (silica gel; methylene chloride:methanol=9:1)

[3261] HPLC/MS (method F): RT=3.58 min.; [M+H]+=495; Abs. λ max=264,6 nm

[3262] (17)N-(3-[4-(2-acetylamino-ethylamino)-5-trifluoromethyl-pyrimidin-2-ylamino]-phenyl)-3,5-difluoro-benzamide

[3263] Prepared from compound 2 (67).

[3264] Melting point: 231° C.

[3265] R_(f)=0,24 (silica gel; methylene chloride:methanol=9:1)

[3266] HPLC/MS (method F): RT=4,00 min.; [M+H]+=495; Abs. λ max=262,7 nm

EXAMPLE 11

[3267]N-{2-[2-(3-piperidin-1-ylmethyl-phenylamino)-5-trifluoromethyl-pyrimidin-4-ylamino]-ethyl}-acetamide

[3268] 80 mg ofN-{2-[2-(3-formyl-phenylamino)-5-trifluoromethyl-pyrimidin-4-ylamino]-ethyl}-acetamide,1.1 eq. of piperidine and 2 eq. of NaBH(OAc)₃ are dissolved in 2 ml ofTHF and the mixture is stirred overnight at ambient temperature. Thereaction is stopped by the addition of 2 ml of saturated aqueous sodiumcarbonate solution and extracted twice with 10 ml of methylene chloride.The organic phase is washed with water, dried over sodium sulphate andevaporated to dryness. The crude product is purified over silica gelwith methylene chloride/methanol.

[3269] Melting point: 154-155° C.

[3270] R_(f)=0.11 (silica gel; methylene chloride:methanol=9:1)

[3271] HPLC/MS (method F): RT=3,35 min.; [M+H]+=437; Abs. λ max=253 nm

[3272] The following compounds are obtained analogously to Example 11:

[3273] (1)N-(2-{2-[3-(3-oxo-piperazin-1-ylmethyl)-phenylamino]-5-trifluoromethyl-pyrimidin-4-ylamino}-ethyl)-acetamide

[3274] Melting point: 196-198° C.

[3275] R_(f)=0,23 (silica gel; methylene chloride:methanol=9:1)

[3276] HPLC/MS (method F): RT=3,14 min.; [M+H]+=452; Abs. λ max=255 nm

[3277] (2)N-{2-[2-(3-pyrrolidin-1-ylmethyl-phenylamino)-5-trifluoromethyl-pyrimidin-4-ylamino]-ethyl}-acetamide

[3278] Melting point: 172-173° C.

[3279] R_(f)=0.16 (silica gel; methylene chloride:methanol=85:15)

[3280] HPLC/MS (method F): RT=3,25 min.; [M+H]+=423; Abs. λ max=255 nm

[3281] (3)N-{2-[2-(3-dimethylaminomethyl-phenylamino)-5-trifluoromethyl-pyrimidin-4-ylamino]-ethyl}-acetamide

[3282] Melting point: 140-141° C.

[3283] R_(f)=0,21 (silica gel; methylene chloride:methanol=85:15)

[3284] HPLC/MS (method F): RT=3,22 min.; [M+H]+=397; Abs. λ max=253 nm

[3285](4)1-{3-[2-(3-dimethylaminomethyl-phenylamino)-5-trifluoromethyl-pyrimidin-4-ylamino]-propyl}-pyrrolidin-2-one

[3286] Melting point: 126-128° C.

[3287] R_(f)=0.19 (silica gel; methylene chloride:methanol=9:1)

[3288] HPLC/MS (method F): RT=3,43 min.; [M+H]+=437; Abs. λ max=253 nm

[3289](5)1-{3-[2-(3-pyrrolidin-1-ylmethyl-phenylamino)-5-trifluoromethyl-pyrimidin-4-ylamino]-propyl}-pyrrolidin-2-one

[3290] Melting point: 122-124° C.

[3291] R_(f)=0.14 (silica gel; methylene chloride:methanol=9:1)

[3292] HPLC/MS (method F): RT=3,5 min.; [M+H]+=463; Abs. λ max=253 nm

[3293](6)1-{3-[2-(3-piperidin-1-ylmethyl-phenylamino)-5-trifluoromethyl-pyrimidin-4-ylamino]-propyl}-pyrrolidin-2-one

[3294] Melting point: 130-132° C.

[3295] R_(f)=0,23 (silica gel; methylene chloride:methanol=9:1)

[3296] HPLC/MS (method F): RT=3,52 min.; [M+H]+=477; Abs. λ max=253 nm

[3297] (7)1-{3-[2-(4-dimethylaminomethyl-phenylamino)-5-trifluoromethyl-pyrimidin-4-ylamino]-propyl}-pyrrolidin-2-one

[3298] Melting point: 93-95° C.

[3299] R_(f)=0,09 (silica gel; methylene chloride:methanol=9:1)

[3300] HPLC/MS (method G): RT=3,03 min.; [M+H]+=437; Abs. λ max=259 nm

[3301] (8)N-[2-(2-{4-[(isobutyl-methyl-amino)-methyl]-phenylamino}-5-trifluoromethyl-pyrimidin-4-ylamino)-ethyl]-acetamide

[3302] Melting point: 162-163° C.

[3303] R_(f)=0,38 (silica gel; methylene chloride:methanol=85:15)

[3304] HPLC/MS (method G): RT=3,11 min.; [M+H]+=439; Abs. λ max 255 nm

[3305] (9)N-{2-[2-(4-pyrrolidin-1-ylmethyl-phenylamino)-5-trifluoromethyl-pyrimidin-4-ylamino]-ethyl}-acetamide

[3306] Melting point: 170-173° C.

[3307] R_(f)=0.18 (silica gel; methylene chloride:methanol=85:15)

[3308] HPLC/MS (method G): RT=2,83 min.; [M+H]+=423; Abs. λ max=261 nm

[3309](10)1-{3-[2-(4-pyrrolidin-1-ylmethyl-phenylamino)-5-trifluoromethyl-pyrimidin-4-ylamino]-propyl}-pyrrolidin-2-one

[3310] Melting point: 122-125° C.

[3311] R_(f)=0,23 (silica gel; methylene chloride:methanol=85:15)

[3312] HPLC/MS (method G): RT=3,11 min.; [M+H]+=463; Abs. λ max=263 nm

[3313](11)1-{3-[2-(4-Morpholin-4-ylmethyl-phenylamino)-5-trifluoromethyl-pyrimidin-4-ylamino]-propyl}-pyrrolidin-2-one

[3314] Melting point: 128-130° C.

[3315] R_(f)=0.51 (silica gel; methylene chloride:methanol=9:1)

[3316] HPLC/MS (method G): RT=3,02 min.; [M+H]+=479; Abs. λ max=259 nm

[3317](12)1-(3-{2-[4-(3,5-dimethyl-piperazin-1-ylmethyl)-phenylamino]-5-trifluoromethyl-pyrimidin-4-ylamino}-propyl)-pyrrolidin-2-one

[3318] Melting point: 83-85° C.

[3319] R_(f)=0.11 (silica gel; methylene chloride:methanol=9:1)

[3320] HPLC/MS (method G): RT=2,95 min.; [M+H]+=506; Abs. λ max=265 nm

[3321] (13)N-[2-(2-{3-[(diisopropylamino)-methyl]-phenylamino}-5-trifluoromethyl-pyrimidin-4-ylamino)-ethyl]-acetamide

[3322] Melting point: 60-63° C.

[3323] R_(f)=0,21 (silica gel; methylene chloride:methanol=9:1)

[3324] HPLC/MS (method F): RT=3,03 min.; [M+H]+=453; Abs. λ max=253 nm

[3325](14)1-(3-{2-[4-(4-acetyl-piperazin-1-ylmethyl)-phenylamino]-5-trifluoromethyl-pyrimidin-4-ylamino}-propyl)-pyrrolidin-2-one

[3326] Melting point: 163-163° C.

[3327] R_(f)=0.46 (silica gel; methylene chloride:methanol=9:1)

[3328] HPLC/MS (method F): RT=3,00 min.; [M+H]+=520; Abs. λ max=263 nm

[3329] (15)N-{2-[2-(4-methylaminomethyl-phenylamino)-5-trifluoromethyl-pyrimidin-4-ylamino]-ethyl}-acetamide

[3330] Melting point: 130-132° C.

[3331] R_(f)=0,05 (silica gel; methylene chloride:methanol=8:2)

[3332] HPLC/MS (method F): RT=2,8 min.; [M+H]+=383; Abs. λ max=261 nm

[3333](16)1-[3-(2-{3-[(diisopropylamino)-methyl]-phenylamino}-5-trifluoromethyl-pyrimidin-4-ylamino)-propyl]-pyrrolidin-2-one

[3334] Melting point: 141-143° C.

[3335] R_(f)=0,37 (silica gel; methylene chloride:methanol=9:1)

[3336] HPLC/MS (method F): RT=3,24 min.; [M+H]+=493; Abs. λ max=249 nm

[3337](17)1-{3-[2-(3-methylaminomethyl-phenylamino)-5-trifluoromethyl-pyrimidin-4-ylamino]-propyl}-pyrrolidin-2-one

[3338] Melting point: 65-68° C.

[3339] HPLC/MS (method F): RT=2,98 min.; [M+H]+=423; Abs. λ max=251 nm

[3340] (18)N-[2-(2-{4-[(diisopropylamino)-methyl]-phenylamino}-5-trifluoromethyl-pyrimidin-4-ylamino)-ethyl]-acetamide

[3341] Melting point: 140-143° C.

[3342] R_(f)=0,26 (silica gel; methylene chloride:methanol=85:15)

[3343] HPLC/MS (method F): RT=3,04 min.; [M+H]+=453; Abs. λ max=251 nm

[3344] (19)N-{2-[2-(3-methylaminomethyl-phenylamino)-5-trifluoromethyl-pyrimidin-4-ylamino]-ethyl}-acetamide

[3345] Melting point: 137-140° C.

[3346] R_(f)=0,09 (silica gel; methylene chloride:methanol=9:1)

[3347] HPLC/MS (method F): RT=2,77 min.; [M+H]+=383; Abs. λ max=253 nm

[3348] (20)1-[3-(2-{4-[(isobutyl-methyl-amino)-methyl]-phenylamino}-5-trifluoromethyl-pyrimidin-4-ylamino)-propyl]-pyrrolidin-2-one

[3349] Melting point: 110-113° C.

[3350] R_(f)=0,36 (silica gel; methylene chloride:methanol=9:1)

[3351] HPLC/MS (method G): RT=3,31 min.; [M+H]+=479; Abs. λ max=265 nm

[3352] (21)N-{2-[2-(4-Azepan-1-ylmethyl-phenylamino)-5-trifluoromethyl-pyrimidin-4-ylamino]-ethyl}-acetamide

[3353] Melting point: 170-172° C.

[3354] R_(f)=0.11 (silica gel; methylene chloride:methanol=85:15)

[3355] HPLC/MS (method G): RT=3,07 min.; [M+H]+=451; Abs. λ max=263 nm

[3356](22)1-{3-[2-(4-Azepan-1-ylmethyl-phenylamino)-5-trifluoromethyl-pyrimidin-4-ylamino]-propyl}-pyrrolidin-2-one

[3357] Melting point: 142-145° C.

[3358] R_(f)=0.19 (silica gel; methylene chloride:methanol=85:15)

[3359] HPLC/MS (method G): RT=3,31 min.; [M+H]+=491; Abs. λ max=265 nm

[3360] (23)N-(2-{2-[4-(isobutylamino-methyl)-phenylamino]-5-trifluoromethyl-pyrimidin-4-ylamino}-ethyl)-acetamide

[3361] Melting point: 163-165° C.

[3362] R_(f)=0.13 (silica gel; methylene chloride:methanol=9:1)

[3363] HPLC/MS (method G): RT=3,06 min.; [M+H]+=; 425 Abs. λ max=261 nm

[3364] (24)1-{3-[5-methyl-2-(4-piperidin-1-ylmethyl-phenylamino)-pyrimidin-4-ylamino]-propyl}-pyrrolidin-2-one

[3365] Melting point: 144-145° C.

[3366] R_(f)=0.10 (silica gel; methylene chloride:methanol=8:2)

[3367] HPLC/MS (method F): RT=2,12 min.; [M+H]+=423; Abs. λ max=263 nm

[3368] (25)1-(3-{2-[4-(isobutylamino-methyl)-phenylamino]-5-trifluoromethyl-pyrimidin-4-ylamino}-propyl)-pyrrolidin-2-one

[3369] Melting point: 112-114° C.

[3370] R_(f)=0,21 (silica gel; methylene chloride:methanol=9:1)

[3371] HPLC/MS (method G): RT=3,28 min.; [M+H]+=465; Abs. ? max=261 nm

[3372] (26)N-(2-{2-[4-(3,5-dimethyl-piperazin-1-ylmethyl)-phenylamino]-5-trifluoromethyl-pyrimidin-4-ylamino}-ethyl)-acetamide

[3373] Melting point: 186-189° C.

[3374] R_(f)=0.10 (silica gel; methylene chloride:methanol=85:15)

[3375] HPLC/MS (method F): RT=3 min.; [M+H]+=466; Abs. λ max=261 nm

[3376] (27)N-{2-[5-Chloro-2-(4-piperidin-1-ylmethyl-phenylamino)-pyrimidin-4-ylamino]-ethyl}-acetamide

[3377] Melting point: 162-164° C.

[3378] R_(f)=0,25 (silica gel; methylene chloride:methanol=4:1)

[3379] HPLC/MS (method F): RT=2,88 min.; [M+H]+=; 403 Abs. λ max=267 nm

[3380] (28)N-(2-{2-[4-(4-acetyl-piperazin-1-ylmethyl)-phenylamino]-5-trifluoromethyl-pyrimidin-4-ylamino}-ethyl)-acetamide

[3381] Melting point: 80-83° C.

[3382] R_(f)=0,31 (silica gel; methylene chloride:methanol=9:1)

[3383] HPLC/MS (method F): RT=3,01 min.; [M+H]+=480; Abs. λ max=257 nm

[3384] (29)1-{3-[2-(4-methylaminomethyl-phenylamino)-5-trifluoromethyl-pyrimidin-4-ylamino]-propyl}-pyrrolidin-2-one

[3385] HPLC/MS (method F): RT=2,28 min.; [M+H]+=423; Abs. λ max=261 nm

[3386](30)1-(3-{2-[4-(2,5-dimethyl-pyrrolidin-1-ylmethyl)-phenylamino]-5-trifluoromethyl-pyrimidin-4-ylamino}-propyl)-pyrrolidin-2-one

[3387] Melting point: 131-134° C.

[3388] R_(f)=0.18 (silica gel; methylene chloride:methanol=9:1)

[3389] HPLC/MS (method G): RT=3,09 min.; [M+H]+=491; Abs. λ max=263 nm

[3390](31)1-{3-[2-(3-Morpholin-4-ylmethyl-phenylamino)-5-trifluoromethyl-pyrimidin-4-ylamino]-propyl}-pyrrolidin-2-one

[3391] Melting point: 132-135° C.

[3392] R_(f)=0.47 (silica gel; methylene chloride:methanol=9:1)

[3393] HPLC/MS (method G): RT=2,88 min.; [M+H]+=479; Abs. λ max=253 nm

[3394] (32)1-[3-(2-{4-[(diisopropylamino)-methyl]-phenylamino}-5-trifluoromethyl-pyrimidin-4-ylamino)-propyl]-pyrrolidin-2-one

[3395] Melting point: 121° C.

[3396] R_(f)=0,31 (silica gel; methylene chloride:methanol=9:1)

[3397] HPLC/MS (method F): RT=3,42 min.; [M+H]+=493; Abs. λ max=263 nm

[3398] (33)N-{2-[2-(3-Morpholin-4-ylmethyl-phenylamino)-5-trifluoromethyl-pyrimidin-4-ylamino]-ethyl}-acetamide

[3399] Melting point: 169-170° C.

[3400] R_(f)=0.443 (silica gel; methylene chloride:methanol=9:1)

[3401] HPLC/MS (method F): RT=2,53 min.; [M+H]+=439; Abs. ? max=255 nm

[3402](34)1-[3-(2-{3-[(2,2,2-Trifluoro-ethylamino)-methyl]-phenylamino}-5-trifluoromethyl-pyrimidin-4-ylamino)-propyl]-pyrrolidin-2-one

[3403] Melting point: 93-94° C.

[3404] R_(f)=0,61 (silica gel; methylene chloride:methanol=9:1)

[3405] HPLC/MS (method E): RT=2,92 min.; [M+H]+=491; Abs. λ max=253 nm

[3406] (35)N-[2-(2-{3-[(2,2,2-Trifluoro-ethylamino)-methyl]-phenylamino}-5-trifluoromethyl-pyrimidin-4-ylamino)-ethyl]-acetamide

[3407] Melting point: 139-144° C.

[3408] R_(f)=0.44 (silica gel; methylene chloride:methanol=9:1)

[3409] HPLC/MS (method E): RT=3,11 min.; [M+H]+=451; Abs. λ max=255 nm

[3410] (36)1-[3-(2-{4-[(2,2,2-Trifluoro-ethylamino)-methyl]-phenylamino}-5-trifluoromethyl-pyrimidin-4-ylamino)-propyl]-pyrrolidin-2-one

[3411] Melting point: 92-98° C.

[3412] R_(f)=0,61 (silica gel; methylene chloride:methanol=9:1)

[3413] HPLC/MS (method E): RT=3,23 min.; [M+H]+=491; Abs. λ max=251 nm

[3414] (37)N-[2-(2-{4-[(2,2,2-Trifluoro-ethylamino)-methyl]-phenylamino}-5-trifluoromethyl-pyrimidin-4-ylamino)-ethyl]-acetamide

[3415] Melting point: 156-165° C.

[3416] R_(f)=0.45 (silica gel; methylene chloride:methanol=9:1)

[3417] HPLC/MS (method E): RT=2,92 min.; [M+H]+=451; Abs. λ max=257 nm

EXAMPLE 12

[3418] Preparation of Recombinant Cyclin-CDK Enzymes

[3419] The corresponding cDNAs for human cyclin B 1 (cyclin E, or.cyclin D1) and human CDK1 (CDK2, or. CDK4) were cloned by standardmethods using RT-PCR, and cloned into a transfer vector (cyclin inpAcG2T made by Pharmingen, CDKs in p2Bac made by Invitrogen) for thebaculovirus system. Recombinant cyclin B 1-CDK1 (or cyclin E-CDK2,cyclin D1-CDK4) was expressed in High Five insect cells (Trichoplusiani) by coinfection with both recombinant baculoviruses (after the 4thround of amplification, >1×10⁸ viruses/ml). 72 h after the infection theHigh Five cells were harvested, and deep-frozen in liquid nitrogen.After thawing the cells were resuspended in lysing buffer (50 mM HEPESpH 7.5, 10 mM MgCl₂, 1 mM DTT, 5 μg/ml leupeptin, 5 μg/ml aprotinin, 100μM NaF, 100 μM PMSF, 10 mM β-glycerolphosphate, 100 μM Na₃VO₄, 30 mMnitrophenylphosphate, 17.5 ml of lysing buffer per 10⁸ cells) andincubated on ice for 30 min. The cell lysate was freed from the celldebris by centrifugation and the quantity of recombinant cyclin B1-CDK1enzyme (or cyclin E-CDK2, cyclin D1-CDK4) in the total lysate (about 1-5mg/ml) was determined by SDS-polyacrylamide gel electrophoresis. CyclinD1-CDK4 was purified by means of a GST-tag on cyclin D1 and then usingglutathione beads (total protein about 0.2 mg/ml).

EXAMPLE 13

[3420] Cyclin B 1-CDK1 Kinase Inhibition Test

[3421] All the kinase tests were carried out in 96-well microtitreplates (Greiner PS) in a final volume of 60 μl. The kinase testcontained 1% DMSO (v/v), 5 μg of histone H1 (calf thymus, RocheMolecular Biochemicals), 1 to 5 μg of a cell lysate with recombinantcyclin B1/CDK1, the test substance (in a final concentration of 1 nM to10 μM) and kinase buffer (15 mM MgCl2, 25 mM MOPS, pH 7.0, 0.1 mM DTT).As a negative control the kinase reaction was carried out in the absenceof the substrate histone H1. As a positive control the kinase reactionwas carried out in the absence of a test substance. As an internalcontrol 30 μM and 300 μM (final concentration) of the kinase inhibitorolomoucin (Alexis) were used.

[3422] The PS microtitre plates were placed on ice, and 10 μl of thetest substance, in different concentrations (in each case in 6% DMSO),20 μl of the histone H1 (250 μg/ml in kinase buffer) and 20 μl of cyclinB1/CDK1 (1 to 5 fig of the recombinant cell lysate in 20 μl of kinasebuffer) were pipetted in and mixed together. The kinase reaction isstarted by the addition of 10 μl of ATP mix (0.045 mM ATP, 0.5 μCi³³P-ATP in kinase buffer) and incubated for 30 min at 30° C. and 600 rpmin a shaking incubator. After incubation the plates were placed on iceand the proteins were precipitated by the addition of 125 μl of ice-cold5% trichloroacetic acid. After 15 min on ice the precipitates weretransferred onto Packard Unifilter 96 GF/B plates with the PackardHarvester System, and collected by vacuum filtration. The precipitateswere washed 4 times with dist. H₂O at ambient temperature. The filterplates were then dried at 60° C. and 50 μl of scintillation liquid wereadded to each well (Ultima Gold, Packard). The plate was sealed up withSealing Tape and after 1 h measured in a scintillation measuringapparatus (Micro Beta made by Wallac).

[3423] The inhibition of the substances was calculated as a percentageof the control (cyclin B1-CDK1 without inhibitor) and the activesubstance concentration which inhibits the enzyme activity by 50% (IC50)was derived.

EXAMPLE 14

[3424] Cyclin E-CDK2 Kinase Inhibition Test

[3425] The Inhibition Test with Cyclin E-CDK2 was Carried Out Using theSame Method as for Cyclin B1-CDK1, Except that Recombinant Cyclin E-CDK2was Used as the Enzyme

EXAMPLE 15

[3426] Cyclin D1-CDK4 Kinase Inhibition Test

[3427] For the inhibition test with cyclin D1-CDK4, recombinantRetinoblastoma Protein (pRB) from aa379-928, which contains a GST-tag atthe N-terminus, was used as the substrate. GST-pRB was expressed inbacteria and then purified using glutathione beads (about 0.2 mg/ml).

[3428] The kinase test contained 1% DMSO (v/v), 10 μg pRB, 0.4 μg of acell lysate with recombinant cyclin D1-CDK4, the test substance (finalconcentration from 1 nM to 10 μM) and kinase buffer (15 mM MgCl2, 25 mMMOPS, pH 7.0, 0.1 mM DTT). As a negative control the kinase reaction wascarried out in the absence of the substrate pRB. As a positive controlthe kinase reaction was carried out in the absence of a test substance.As an internal control 30 μM and 300 μM (final concentration) of thekinase inhibitor olomoucin (Alexis) were used.

[3429] The PS microtitre plates were placed on ice, and 10 μl of thetest substance, in different concentrations (in each case in 6% DMSO),20 μl of pRB (10 μg in kinase buffer) and 20 μl of cyclin D1-CDK4 (0.4μg of the recombinant cell lysate in 20 μl of kinase buffer) werepipetted in and mixed together. The kinase reaction was started by theaddition of 10 μl of ATP mix (0.045 mM ATP, 1 μCi ³³P-ATP i n kinasebuffer) and incubated for 45 min at 32° C. and 600 rpm in a vibratingincubator. After incubation, 50 μl of the reaction mixture were pipettedonto P81 filters (Whatmann). After 20 sec reaction time the filters werewashed 4 times with 1.5% phosphoric acid (about 5 min per washing step)while shaking them gently. After washing the filters were dried at 85°C., scintillation liquid was added and the scintillation was measured ina scintillation counter (Micro Beta made by Wallac).

EXAMPLE 16

[3430] Measurement of the Cytotoxicity on Cultivated Human Tumour Cells

[3431] Cells of the non-small cell lung tumour cell line NCI H-460(obtained from American Type Culture Collection (ATCC)) were cultivatedin RPMI 1640 medium (Gibco) and 10% foetal calf serum (Gibco) andharvested in the log growth phase. Then the NCI H-460 cells were placedin 96-well plates (Costar) at a density of 1000 cells per well andincubated overnight in an incubator (at 37° C. and 5% CO₂), each platecontaining 6 wells which were filled only with medium (3 wells as amedium control and 3 wells for incubation with reduced AlamarBlue). Theactive substances were added to the cells in various concentrations(dissolved in DMSO; final concentration: 1%) (each measurement beingdone three times). After 72 hours incubation 20 μl AlamarBlue (AccuMedInternational) were added to each well, and the cells were incubated fora further 5 hours. As a control 20 μl of reduced Alamar Blue were addedto three wells (AlamarBlue Reagent autoclaved for 30 min). After 5 hincubation the colour change of the AlamarBlue Reagent in the individualwells was determined in an Perkin Elmer Fluorescence spectrophotometer(excitation 530 nm, emission 590 nm, slits 15, integrate time 0.1). Thequantity of AlamarBlue Reagent reacted represents the metabolic activityof the cells. The relative cell activity was calculated as a percentageof the control (NCI H-460 cells without an inhibitor) and the activesubstance concentration which inhibits the cell activity by 50% (IC50)was derived. The values were calculated from the average of threeseparate measurements, correcting for the control value (mediumcontrol).

[3432] Abbreviations Used:

[3433] ATP Adenosine triphosphate

[3434] Ci Curie

[3435] DTT 1,4-dithiothreitol

[3436] DMSO dimethylsulphoxide

[3437] GST Glutathion-S-transferase

[3438] HEPES N-2-hydroxyethylpiperazine-N′-2′-ethanesulphonic acid

[3439] MOPS 3-(N-morpholino)-propanesulphonic acid

[3440] NaF sodium fluoride

[3441] PMSF phenylmethylsulphonyl fluoride

[3442] The following compounds according to the invention have aCDK1/cyclinB1 IC₅₀ value of less than 100 nM in the CDK1 tests (Example13):

EXAMPLE 1

[3443] Serial numbers: 003, 004, 005, 008, 009, 010, 011, 012, 014, 015,016, 017, 018, 019, 020, 021, 022, 023, 024, 025, 026, 027, 028, 029,030, 031, 032, 033, 034, 035, 037, 038, 039, 040, 041, 042, 043, 044,045, 046, 047, 049, 050, 052, 053, 054, 055, 067, 073, 077, 079, 080,088, 093, 104, 107, 109, 111, 112, 113, 115, 116, 117, 118, 119, 120,152, 304, 349, 388, 585, 628, 651, 652, 654, 655, 656, 661, 662, 663,683, 685, 689, 690, 692, 693, 694, 695

EXAMPLE 2

[3444] Serial numbers: 002, 003, 004, 007, 008, 009, 010, 011, 012, 013,014, 015, 016, 036, 037, 038, 041, 042, 043, 044, 045, 046, 047, 048,051, 052, 053, 057, 058, 059, 060, 061, 062, 075, 076, 106,109, 134,136, 141, 142

EXAMPLE 4

[3445] Serial number: 001

EXAMPLE 5

[3446] Serial number: 000

EXAMPLE 7

[3447] Serial numbers: 001, 002, 006, 010, 012, 013, 015, 021, 022, 024,027, 028, 029, 032, 035, 036

EXAMPLE 8

[3448] Serial numbers: 003, 007, 024, 026, 028

EXAMPLE 9

[3449] Serial number: 001

EXAMPLE 10

[3450] Serial numbers: 000, 014, 015, 016

EXAMPLE 11

[3451] Serial number: 034

[3452] Preparations for Administration

[3453] The compounds according to the invention may be administered byoral, transdermal or parenteral route or by inhalation. The compoundsaccording to the invention are present as active ingredients inconventional preparations, e.g. in compositions consisting essentiallyof an inert pharmaceutical carrier and an effective dose of the activesubstance, such as for example plain or coated tablets, capsules,lozenges, powders, solutions, suspensions, emulsions, syrups,suppositories, transdermal systems, etc. An effective dose of thecompounds according to the invention is between 1 and 100, preferablybetween 1 and 50, most preferably between 5-30 mg/dose, for oraladministration, and between 0.001 and 50, preferably between 0.1 and 10mg/dose for intravenous or intramuscular administration. For inhalation,solutions containing 0.01 to 1.0, preferably 0.1 to 0.5% of activesubstance are suitable according to the invention. For inhalation, theuse of powders is preferred. It is also possible to use the compoundsaccording to the invention as a solution for infusion, preferably inphysiological saline or nutrient salt solution.

[3454] The compounds according to the invention may be used on their ownor in conjunction with other active substances according to theinvention, optionally also in conjunction with other pharmacologicallyactive substances. Suitable preparations include for example tablets,capsules, suppositories, solutions, elixirs, emulsions or dispersiblepowders. Suitable tablets may be obtained, for example, by mixing theactive substance(s) with known excipients, for example inert diluentssuch as calcium carbonate, calcium phosphate or lactose, disintegrantssuch as corn starch or alginic acid, binders such as starch or gelatine,lubricants such as magnesium stearate or talc and/or agents for delayingrelease, such as carboxymethyl cellulose, cellulose acetate phthalate,or polyvinyl acetate. The tablets may also comprise several layers.

[3455] Coated tablets may be prepared accordingly by coating coresproduced analogously to the tablets with substances normally used fortablet coatings, for example collidone or shellac, gum arabic, talc,titanium dioxide or sugar. To achieve delayed release or preventincompatibilities the core may also consist of a number of layers.Similarly the tablet coating may consist of a number of layers toachieve delayed release, possibly using the excipients mentioned abovefor the tablets.

[3456] Syrups or elixirs containing the active substances orcombinations thereof according to the invention may additionally containa sweetener such as saccharine, cyclamate, glycerol or sugar and aflavour enhancer, e.g. a flavouring such as vanilline or orange extract.They may also contain suspension adjuvants or thickeners such as sodiumcarboxymethyl cellulose, wetting agents such as, for example,condensation products of fatty alcohols with ethylene oxide, orpreservatives such as p-hydroxybenzoates.

[3457] Solutions for injection and infusion are prepared in the usualway, e.g. with the addition of preservatives such as p-hydroxybenzoates,or stabilisers such as alkali metal salts of ethylenediamine tetraaceticacid, and transferred into injection vials or ampoules.

[3458] Capsules containing one or more active substances or combinationsof active substances may for example be prepared by mixing the activesubstances with inert carriers such as lactose or sorbitol and packingthem into gelatine capsules.

[3459] Suitable suppositories may be made for example by mixing withcarriers provided for this purpose, such as neutral fats orpolyethyleneglycol or the derivatives thereof.

[3460] A therapeutically effective daily dose is between 1 and 800 mg,preferably 10-300 mg, in adults.

[3461] The Examples that follow illustrate the present inventionwithout, however, restricting its scope.

[3462] Examples of Pharmaceutical Formulations A) Tablets per tabletactive substance 100 mg lactose 140 mg corn starch 240 mgpolyvinylpyrrolidone  15 mg magnesium stearate  5 mg 500 mg

[3463] The finely ground active substance, lactose and some of the cornstarch are mixed together. The mixture is screened, then moistened witha solution of polyvinylpyrrolidone in water, kneaded, wet-granulated anddried. The granules, the remaining corn starch and the magnesiumstearate are screened and mixed together. The mixture is compressed toproduce tablets of suitable shape and size. B) Tablets per tablet activesubstance 80 mg lactose 55 mg corn starch 190 mg  microcrystallinecellulose 35 mg polyvinylpyrrolidone 15 mg sodium-carboxymethyl starch23 mg magnesium stearate  2 mg 400 mg 

[3464] The finely ground active substance, some of the corn starch,lactose, microcrystalline cellulose and polyvinylpyrrolidone are mixedtogether, the mixture is screened and worked with the remaining cornstarch and water to form a granulate which is dried and screened. Thesodiumcarboxymethyl starch and the magnesium stearate are added andmixed in and the mixture is compressed to form tablets of a suitablesize. C) Coated tablets per coated tablet Active substance  5 mg Cornstarch 41.5 mg   Lactose 30 mg Polyvinylpyrrolidone  3 mg Magnesiumstearate 0.5 mg  80 mg

[3465] The active substance, corn starch, lactose andpolyvinylpyrrolidone are thoroughly mixed and moistened with water. Themoist mass is pushed through a screen with a 1 mm mesh size, dried atabout 45° C. and the granules are then passed through the same screen.After the magnesium stearate has been mixed in, convex tablet cores witha diameter of 6 mm are compressed in a tablet-making machine. The tabletcores thus produced are coated in known manner with a coveringconsisting essentially of sugar and talc. The finished coated tabletsare polished with wax. D) Capsules per capsule Active substance 50 mgCorn starch 268.5 mg   Magnesium stearate 1.5 mg  320 mg 

[3466] The substance and corn starch are mixed and moistened with water.The moist mass is screened and dried. The dry granules are screened andmixed with magnesium stearate. The finished mixture is packed into size1 hard gelatine capsules. E) Ampoule solution active substance 50 mgsodium chloride 50 mg water for inj.  5 ml

[3467] The active substance is dissolved in water at its own pH oroptionally at pH 5.5 to 6.5 and sodium chloride is added to make itisotonic. The solution obtained is filtered free from pyrogens and thefiltrate is transferred under aseptic conditions into ampoules which arethen sterilised and sealed by fusion. The ampoules contain 5 mg, 25 mgand 50 mg of active substance.

[3468] F) Suppositories

[3469] Active substance 50 mg

[3470] Solid fat 1650 mg

[3471] 1700 mg

[3472] The hard fat is melted. At 40° C. the ground active substance ishomogeneously dispersed. It is cooled to 38° C. and poured into slightlychilled suppository moulds.

1. A trisubstituted pyrimidine of formula (I):

wherein R_(a) denotes a hydrogen atom or an alkyl group, R_(b) denotesan aralkyl group optionally substituted in the alkylene moiety by one ortwo alkyl groups, which may be substituted in the aryl moiety by acarboxy, alkoxycarbonyl, aminocarbonyl, alkylaminocarbonyl,dialkylaminocarbonyl, amino, alkylamino, dialkylamino, cyano,trifluoromethyl or nitro group or one or two fluorine, chlorine, bromineor iodine atoms or one or two hydroxy, alkyl or alkoxy groups, while thesubstituents may be identical or different, or by a 5- to 7-memberedalkyleneimino group, while in each case one or two methylene groupsadjacent to the nitrogen atom may be replaced in each case by a carbonylgroup or in the abovementioned 6- to 7-membered alkyleneimino groups amethylene group in the 4-position may be replaced by an oxygen atom, byan imino, N-aryl-imino or N-alkyl-imino group, or denotes a phenyl groupoptionally substituted by the groups R₁ to R₃, while R₁ and R₂ in eachcase independently of one another denote a fluorine, chlorine, bromineor iodine atom, or a C₁₋₂-alkyl or hydroxy group, a C₃₋₇-cycloalkyl orC₄₋₇-cycloalkoxy group which may be substituted in each case by one ortwo alkyl groups or by an aryl group, a C₂₋₅-alkenyl group optionallysubstituted by an aryl group, a C₂₋₅-alkynyl group optionallysubstituted by an aryl group an aryl, aryloxy, aralkyl, aralkoxy,alkylsulphenyl, alkylsulphinyl, alkylsulphonyl, alkylsulphonyloxy,trifluoromethylsulphenyl, trifluoromethylsulphinyl,trifluoromethylsulphonyl, arylsulphenyl, arylsulphinyl, arylsulphonyl,aralkylsulphenyl, aralkylsulphinyl or aralkylsulphonyl group, a methylor methoxy group substituted by 1 to 3 fluorine atoms, a C₂₋₄-alkyl orC₂₋₄-alkoxy group substituted by 1 to 5 fluorine atoms, a nitro, amino,alkylamino, dialkylamino, C₃₋₇-cycloalkylamino,N-alkyl-C₃₋₇-cycloalkylamino, arylamino, N-alkyl-arylamino, aralkylaminoor N-alkyl-aralkylamino group, a 4- to 7-membered alkyleneimino groupoptionally substituted by 1 to 4 alkyl groups, while in theabovementioned 5- to 7-membered alkyleneimino groups in each case one ortwo methylene groups adjacent to the nitrogen atom may be replaced ineach case by a carbonyl group or in the abovementioned 6- to 7-memberedalkyleneimino groups a methylene group in the 4-position may be replacedby an oxygen or sulphur atom, by a sulphinyl, sulphonyl, imino,N-alkylimino, N-alkylcarbonyl-imino, N-alkylsulphonyl-imino,N-arylcarbonyl-imino, N-arylsulphonyi-imino, N-aryl-imino orN-aralkyl-imino group, an (alkyleneimino)carbonyl or(alkyleneimino)sulphonyl group with in each case 4 to 7 cyclic atoms inthe alkyleneimino moiety, optionally substituted by 1 to 4 alkyl groups,while in the abovementioned 6- to 7-membered alkyleneimino moieties ineach case a methylene group in the 4-position may be replaced by anoxygen or sulphur atom, by a sulphinyl, sulphonyl, imino, N-alkyl-imino,N-alkylcarbonyl-imino, N-alkylsulphonyl-imino, N-arylcarbonyl-imino,N-arylsulphonyl-imino, N-aryl-imino or N-aralkyl-imino group, analkylcarbonylamino, N-alkyl-alkylcarbonylamino, alkyl-sulphonylamino,N-alkyl-alkylsulphonylamino, arylcarbonylamino,N-alkyl-arylcarbonylamino, arylsulphonylamino,N-alkyl-arylsulphonylamino, aralkylcarbonylamino,N-alkylaralkylcarbonylamino, aralkylsulphonylamino,N-alkyl-aralkylsulphonylamino, perfluoroalkylsulphonylamino,N-alkyl-perfluoralkylsulphonylamino, alkylcarbonyl, arylcarbonyl,aralkylcarbonyl, aryl-hydroxymethyl, aralkylhydroxymethyl, carboxy,alkoxycarbonyl, aralkoxycarbonyl, aminocarbonyl, alkylaminocarbonyl,dialkylaminocarbonyl, arylaminocarbonyl, N-alkyl-arylaminocarbonyl,aralkylaminocarbonyl, N-alkyl-aralkylaminocarbonyl,N-hydroxy-aminocarbonyl, N-hydroxy-alkylaminocarbonyl,N-alkoxy-aminocarbonyl, N-alkoxy-alkylaminocarbonyl, cyano, azido,N-cyano-amino or N-cyano-alkylamino group, a sulpho, alkoxysulphonyl,aminosulphonyl, alkylaminosulphonyl, dialkylaminosulphonyl,arylaminosulphonyl, pyridylaminosulphonyl, pyrimidinylaminosulphonyl,N-alkyl-arylaminosulphonyl, aralkylaminosulphonyl orN-alkyl-aralkylaminosulphonyl group, a phosphono, O-alkyl-phosphono,O,O′-Dialkyl-phosphono, O-aralkyl-phosphono or O,O′-diaralkyl-phosphonogroup, a C₁₋₂ alkyl group substituted by R₄, wherein R₄ denotes ahydroxy, alkoxy, aryloxy, aralkoxy, amino, alkylamino, haloalkylamino,dialkylamino, alkylsulphenyl, alkylsulphinyl, alkylsulphonyl,arylsulphenyl, arylsulphinyl, arylsulphonyl, aralkylsulphenyl,aralkylsulphinyl, aralkylsulphonyl, carboxy, alkoxycarbonyl,aminocarbonyl, alkylaminocarbonyl, dialkylaminocarbonyl or cyano group,a 4- to 7-membered alkyleneimino group optionally substituted by 1 to 4alkyl groups, while in the abovementioned 5- to 7-membered alkyleneiminogroups one or two methylene groups adjacent to the nitrogen atom may bereplaced in each case by a carbonyl group or in the abovementioned 6- to7-membered alkyleneimino groups a methylene group in the 4-position maybe replaced by an oxygen or sulphur atom, by a sulphinyl, sulphonyl,imino, N-alkyl-imino, N-alkylcarbonyl-imino, N-alkylsulphonyl-imino,N-arylcarbonyl-imino, N-arylsulphonyl-imino, N-aryl-imino orN-aralkyl-imino group, or a 4- to 7-membered alkyleneimino groupoptionally substituted by 1 to 4 alkyl groups, while in theabovementioned 5- to 7-membered alkyleneimino groups in each case one ortwo methylene groups adjacent to the nitrogen atom may be substituted bya carbonyl group or in the abovementioned 6- to 7-membered alkyleneiminogroups may be substituted by one or two hydroxy, alkoxy, aminocarbonyl,alkylaminocarbonyl, dialkylaminocarbonyl, amino, alkylamino anddialkylamino group, an (alkyleneimino)carbonyl group optionallysubstituted by 1 to 4 alkyl groups with 4 to 7 cyclic atoms in thealkyleneimino moiety in each case, while in the abovementioned 6- to7-membered alkyleneimino moieties in each case a methylene group may bereplaced in the 4-position by an oxygen or sulphur atom, by a sulphinyl,sulphonyl, imino, N-alkyl-imino, N-alkylcarbonyl-imino,N-alkylsulphonyl-imino, N-arylcarbonyl-imino, N-arylsulphonyl-imino,N-aryl-imino or N-aralkyl-imino group, or  a group of formula

 wherein h and k, which may be identical or different, represent thenumbers 1 to 3 or h denotes the number 0 and k denotes the number 2, 3or 4, while additionally the above benzo moiety may be mono- ordisubstituted by fluorine, chlorine, bromine or iodine atoms, by alkyl,trifluoromethyl, hydroxy, alkoxy, carboxy or cyano groups, while thesubstituents in each case may be identical or different, and the abovesaturated cyclic alkyleneimino moiety may be substituted by 1 or 2 alkylgroups, R₃ denotes a fluorine, chlorine or bromine atom, a C₁₋₂ alkyl,C₁₋₂ alkoxy or trifluoromethyl group, or a 5 or 6-membered heterocyclic,aromatic ring with at least one nitrogen atom and optionally a sulphuror oxygen atom which may be substituted by one or two alkyl, aryl oraralkyl groups, or a sulpho, alkoxysulphonyl, aminosulphonyl,alkylaminosulphonyl, dialkylaminosulphonyl, arylaminosulphonyl,pyridylaminosulphonyl, pyrimidinylaminosulphonyl,N-alkyl-arylaminosulphonyl, aralkylaminosulphonyl orN-alkyl-aralkylaminosulphonyl group, R₂ together with R₃, if they arebound to adjacent carbon atoms, denote a methylenedioxy group optionallysubstituted by one or two alkyl groups, or an n-C₃₋₆-alkylene groupoptionally substituted by one or two alkyl groups, wherein a methylenegroup may be replaced by an oxygen or sulphur atom, by a sulphinyl,sulphonyl, N-alkylcarbonyl-imino, N-alkylsulphonyl-imino,N-arylcarbonyl-imino or N-arylsulphonyl-imino group, or a1,3-butadiene-1,4-diylene group optionally substituted by one or twofluorine, chlorine, bromine or iodine atoms, by one or two hydroxy,alkyl, alkoxy, trifluoromethyl, carboxy, alkoxycarbonyl, aminocarbonyl,alkylaminocarbonyl, dialkylaminocarbonyl or cyano groups, while thesubstituents may be identical or different, or  a group of formula—(CH₂)_(m)—N(R₅)—(CH₂)_(n)—,  wherein the methylene groups of the cyclicalkyleneimino moieties thus formed may additionally be substituted by 1or 2 alkyl groups, R₅ denotes a hydrogen atom or an alkyl, haloalkyl,aryl or aralkyl group, and m and n, which may be identical or different,represent the numbers 1, 2 or 3, while in the alkyleneimino moietiesthus formed one or two methylene groups adjacent to the nitrogen atommay be replaced in each case by a carbonyl group, or m denotes thenumber 0 and n denotes the number 2, 3 or 4, while in the alkyleneiminomoieties thus formed in each case the methylene group adjacent to thenitrogen atom may be replaced by a carbonyl group, or R2 together withR3 denotes a group of formula-NH—C(═O)—(CH₂)—, —NH—C(═O)—(CH₂)₂,—NH—N═N, —NH—N═CH, —NH—CH═N—, —O—CH═N, —S—CH═N or —NH—CH═CH— and thetautomers of the ring systems defined by —NH—N═N, —NH—N═CH, —NH—CH═N—,while each hydrogen atom may be substituted by an alkyl, aryl or aralkylgroup, or R_(a) together with R₁, if R₁ is in the opposition to thenitrogen atom substituted by R_(a), also denote an n-C₂₋₄-alkylene groupoptionally substituted by one or two alkyl groups, and R_(c)NR_(d)denotes a 4- to 8-membered alkyleneimino group optionally substituted by1 to 4 alkyl groups or 1 to 2 aryl groups, which is additionallysubstituted by the group R₆, while R₆ denotes a carboxy, alkoxycarbonyl,aminocarbonyl, alkylaminocarbonyl, dialkylaminocarbonyl, cyano, hydroxy,alkoxy, aryloxy, aralkoxy, alkylcarbonyloxy, arylcarbonyloxy, amino,alkylamino, hydroxy-C₂₋₄-alkylamino, dialkylamino, cyanamino,formylamino, N-(alkyl)-N-(hydroxy-C₂₋₄-alkyl)amino,bis-(hydroxy-C₂₋₄-alkyl)-amino group, alkylsulphenyl, alkylsulphinyl,alkylsulphonyl, arylsulphenyl, arylsulphinyl, arylsulphonyl,aralkylsulphenyl, aralkylsulphinyl, aralkylsulphonyl, analkylcarbonylamino, N-alkyl-alkylcarbonylamino, alkylsulphonylamino,N-alkyl-alkylsulphonylamino, arylcarbonylamino,N-alkyl-arylcarbonylamino, arylsulphonylamino,N-alkyl-arylsulphonylamino, aralkylcarbonylamino,N-alkyl-aralkylcarbonylamino, aralkylsulphonylamino,N-alkyl-aralkylsulphonylamino, alkoxycarbonylamino,N-alkyl-alkoxycarbonylamino, alkoxycarbonylalkylamino,N-(alkyl)-N-(alkoxycarbonylalkyl)-amino, aralkoxycarbonylamino orN-alkyl-aralkoxycarbonylamino group, an (NR₈R₉)CONR₇ or(NR₈R₉)SO2NR₇-group, wherein R₇, R₈ and R₉, which may be identical ordifferent, in each case denote a hydrogen atom or an alkyl, aryl orpyridyl group, or R₇ and R₈ together denote an n-C₂₋₄-alkylene group andR₉ denotes a hydrogen atom or an alkyl, aryl or pyridyl group, an(alkyleneimino)carbonyl group optionally substituted by 1 to 4 alkylgroups with in each case 4 to 7 cyclic atoms in the alkyleneiminomoiety, while in the abovementioned 6- to 7-membered alkyleneiminomoieties in each case a methylene group in the 4-position may bereplaced by an oxygen or sulphur atom, by a sulphinyl, sulphonyl, imino,N-alkyl-imino, N-alkylcarbonyl-imino, N-alkylsulphonyl-imino,N-aryl-imino or N-aralkyl-imino group, an 4- to 7-membered alkyleneiminogroup optionally substituted by 1 to 4 alkyl groups or a hydroxyalkylgroup, while in the abovementioned 5- to 7-membered alkyleneimino groupsin each case one or two methylene groups adjacent to the nitrogen atommay be replaced by a carbonyl group, a 6 or 7-membered alkyleneiminogroup optionally substituted by 1 to 4 alkyl groups or a hydroxyalkylgroup, while in each case a methylene group in the 4-position of thealkyleneimino moiety is replaced by an oxygen or sulphur atom, by acarbonyl, sulphinyl, sulphonyl, imino, N-alkylimino,N-alkylcarbonyl-imino, N-alkylsulphonyl-imino, N-arylimino orN-aralkyl-imino group and additionally in the alkyleneimino moiety ofthe abovementioned groups in each case one or two of the methylenegroups adjacent to the nitrogen atoms may be replaced by a carbonylgroup, a 4- to 7-membered alkyleneimino group substituted by a hydroxy,alkoxy, amino, alkylamino, dialkylamino, alkylcarbonylamino,N-alkyl-alkylcarbonylamino, alkylsulphonylamino,N-alkyl-alkylsulphonylamino, carboxy, alkoxycarbonyl, aminocarbonyl,alkylaminocarbonyl or dialkylaminocarbonyl group, an alkyl groupsubstituted by a carboxy, alkoxycarbonyl, aminocarbonyl,alkylaminocarbonyl or dialkylaminocarbonyl, cyano, hydroxy, alkoxy,aryloxy, amino, alkylamino, dialkylamino, alkylcarbonylamino,N-alkyl-alkylcarbonylamino, alkoxycarbonylamino,N-alkyl-alkoxycarbonylamino, alkylsulphonylamino,N-alkyl-alkylsulphonylamino, arylcarbonylamino,N-alkyl-arylcarbonylamino, arylsulphonylamino,N-alkyl-arylsulphonylamino, aminocarbonylalkylamino,N-(alkyl)-N-(aminocarbonylalkyl)-amino, alkylaminocarbonylalkylamino,N-(alkyl)-N-(alkylaminocarbonylalkyl)-amino,dialkylaminocarbonylalkylamino,N-(alkyl)-N-(dialkylaminocarbonylalkyl)-amino, dialkylaminoalkoxy,alkylsulphenyl, alkylsulphinyl, alkylsulphonyl, arylsulphenyl,arylsulphinyl or arylsulphonyl group, an (alkyleneimino)alkyl groupoptionally substituted by 1 to 4 alkyl groups with in each case 4 to 7cyclic atoms in the alkyleneimino moiety, while in the abovementioned 6-to 7-membered alkyleneimino moieties a methylene group in the 4-positionmay be replaced in each case by an oxygen or sulphur atom, by asulphinyl, sulphonyl, imino, N-alkyl-imino or N-alkylcarbonyl-iminogroup, an (alkyleneimino)carbonylalkyl group optionally substituted by 1to 4 alkyl groups with in each case 4 to 7 cyclic atoms in thealkyleneimino moiety, while in the abovementioned 6- to 7-memberedalkyleneimino moieties a methylene group in the 4-position may bereplaced in each case by an oxygen or sulphur atom, by a sulphinyl,sulphonyl, imino or N-alkyl-imino group, a (carboxyalkyl)oxy,(alkoxycarbonylalkyl)oxy, (aminocarbonylalkyl)oxy,(alkylaminocarbonylalkyl)oxy or (dialkylaminocarbonylalkyl)oxy group, an[(alkyleneimino)carbonylalkyl]oxy-group optionally substituted by 1 to 4alkyl groups with in each case 4 to 7 cyclic atoms in the alkyleneiminomoiety, while in the abovementioned 6- to 7-membered alkyleneiminomoieties a methylene group in the 4-position may be replaced in eachcase by an oxygen or sulphur atom, by a sulphinyl, sulphonyl, imino orN-alkyl-imino group, a C₅₋₇-cycloalkyl group wherein a methylene groupis replaced by an oxygen or sulphur atom, by a sulphinyl, sulphonyl,imino or N-alkyl-imino, alkylcarbonylimino or alkylsulphonylimino group,a 3,4-dihydro-1H-quinazolin-2-on-3-yl or 1H-benzimidazol-2-on-1-yl-groupoptionally substituted in the aryl moiety by one or two fluorine,chlorine, bromine or iodine atoms or one or two nitro, alkyl, alkoxy orcyano groups in each case, while the substituents may be identical ordifferent, or R_(c)NR_(d) denotes a 6- to 8-membered alkyleneimino groupoptionally substituted by 1 to 4 alkyl groups or by an aryl group, whichmay additionally be substituted by the group R₆, while in theabovementioned alkyleneimino groups a methylene group in the 4-positionis replaced by an oxygen or sulphur atom, by a carbonyl, sulphinyl,sulphonyl, N-oxido-N-alkylimino or R₁₀N-group in each case, while R₁₀denotes a hydrogen atom, an alkyl, hydroxy-C₂₋₄-alkyl,alkoxy-C₂₋₄-alkyl, amino-C₂₋₄-alkyl, alkylamino-C₂₋₄-alkyl,dialkylamino-C₂₋₄-alkyl, (hydroxy-C₂₋₄-alkoxy)-C₂₋₄-alkyl,aminocarbonylalkyl, alkylaminocarbonylalkyl, dialkylaminocarbonylalkyl,aryl, formyl, alkylcarbonyl, alkylsulphonyl, arylcarbonyl,aryl-sulphonyl, aralkylcarbonyl, aralkylsulphonyl, alkoxycarbonyl,aralkoxycarbonyl, cyano, aminocarbonyl, alkylaminocarbonyl ordialkylaminocarbonyl group, an amino-alkylcarbonyl,alkylamino-alkylcarbonyl, dialkylamino-alkylcarbonyl group, an alkylgroup substituted by one, two or three aryl groups, an8-alkyl-8-aza-bicyclo[3.2.1]oct-3-yl group, an aryl or a 2-, 3- or4-pyridyl group or 2-, 4- or 5-pyrimidinyl group an(alkyleneimino)carbonyl or (alkyleneimino)carbonylalkyl group with 4 to7 cyclic atoms in the alkyleneimino moiety in each case, while in theabovementioned 6- to 7-membered alkyleneimino moieties a methylene groupin the 4-position may be replaced in each case by an oxygen or sulphuratom, by a sulphinyl, sulphonyl, imino, N-alkyl-imino,N-alkylcarbonyl-imino or N-aralkyl-imino group, or R_(c)NR_(d) denotes a3-thiazolidinyl-group substituted in the 4-position by a carboxy,alkoxycarbonyl, aminocarbonyl, alkylaminocarbonyl, dialkylaminocarbonylgroup, or R_(c)NR_(d) denotes a 1-pyrrolidinyl group optionallysubstituted by 1 to 4 alkyl groups, wherein two hydrogen atoms on thecarbon skeleton are replaced by a straight-chain alkylene bridge, thisbridge containing 2 to 6 carbon atoms if the two hydrogen atoms arelocated on the same carbon atom, or 1 to 5 carbon atoms if the twohydrogen atoms are located on adjacent carbon atoms, or 2 to 4 carbonatoms if the two hydrogen atoms are located on carbon atoms separated byone atom, while the above-mentioned 1-pyrrolidinyl groups areadditionally substituted by the group R6, which is as hereinbeforedefined, a 1-piperidinyl or 1-azacyclohept-1-yl group optionallysubstituted by 1 to 4 alkyl groups, wherein two hydrogen atoms on thecarbon skeleton are replaced by a straight-chain alkylene bridge, thisbridge containing 2 to 6 carbon atoms if the two hydrogen atoms arelocated on the same carbon atom, or 1 to 5 carbon atoms if the twohydrogen atoms are located on adjacent carbon atoms, or 1 to 4 carbonatoms if the two hydrogen atoms are located on carbon atoms separated byan atom, or 1 to 3 carbon atoms if the two hydrogen atoms are located oncarbon atoms separated by two atoms, while the abovementioned1-piperidinyl- and 1-azacyclohept-1-yl groups are additionallysubstituted by the group R₆, which is as hereinbefore defined, a1-pyrrolidinyl group optionally substituted by 1 to 4 alkyl groups,wherein two hydrogen atoms in the 3 position are substituted by a—O—CH₂CH₂—O or —O—CH₂CH₂CH₂—O-group, a 1-piperidinyl or1-azacyclohept-1-yl group optionally substituted by 1 to 4 alkyl groups,wherein in the 3 position or in the 4 position two hydrogen atoms aresubstituted by a —O—CH₂CH₂—O or —O—CH₂CH₂CH₂—O-group in each case, a1-azetidinyl group optionally substituted by an alkyl group, wherein thetwo hydrogen atoms of a methylene group are replaced by a straight-chainC₄₋₆-alkylene bridge, while in each case a methylene group in theC₄₋₆-alkylene bridge is replaced by a R₁₀N-group, where R₁₀ is ashereinbefore defined, while the bicyclic ring thus formed mayadditionally be substituted by a hydroxy, alkoxy, amino, alkylamino,dialkylamino, cyano, alkylcarbonylamino, alkylsulphonylamino,alkoxycarbonylamino, arylcarbonyl, carboxy, alkoxycarbonyl,aminocarbonyl, alkylaminocarbonyl or dialkylaminocarbonyl group, a1-pyrrolidinyl, 1-piperidinyl or 1-azacyclohept-1-yl group optionallysubstituted by 1 to 2 alkyl groups, wherein the two hydrogen atoms of amethylene group are replaced by a straight-chain C₃₋₆-alkylene bridge,while in each case a methylene group in the C₃₋₆-alkylene bridge isreplaced by a R₁₀N-group, while R₁₀ is as hereinbefore defined, whilethe bicyclic ring thus formed may additionally be substituted by ahydroxy, alkoxy, amino, alkylamino, dialkylamino, cyano,alkylcarbonylamino, alkylsulphonylamino, alkoxycarbonylamino,arylcarbonyl, carboxy, alkoxycarbonyl, aminocarbonyl, alkylaminocarbonylor dialkylaminocarbonyl group, a group of the structure

optionally substituted in the alkylene moieties by 1 or 2 alkyl groups,wherein p and q, which may be identical or different, represent thenumber 1 or 2, and the unit —V=W—X═Y— denotes one of the groups (a),(b), (c), (d) or (e): —N≡C—C≡C— (a), —C═N—C═C— (b), —C═N—N═C— (c),—N═C—C═N— (d), —N═C—N═C— (e),

or —V═W— taken together represent an oxygen or sulphur atom and —X═Y—represents one of the groups —N═C₁-C═N or —C═C—, or —V═W— taken togetherrepresent an imino, N-alkyl-imino, N-aralkyl-imino or N-aryl-imino groupand —X═Y— represents one of the groups —N═N, —N═C, —C═N or —C═C—, or, ifp and q are not the same, —X═Y— taken together represent an oxygen orsulphur atom and —V═W— represents one of the groups —N═C₁-C═N or —C═C—,or —X═Y— taken together represent an imino, N-alkyl-imino,N-aralkyl-imino or N-aryl-imino-group and —V═W— represents one of thegroups —N═N, —N═C₁-C═N or —C═C—, while one or two of the availablecarbon atoms of the unit —V═W—X═Y— may be substituted in each case by ahydroxy, alkoxy, amino, alkylamino, dialkylamino, carboxy,alkoxycarbonyl, aminocarbonyl, alkylaminocarbonyl, dialkylaminocarbonylor hydrazinocarbonyl group, while the substituents may be identical ordifferent, and the remaining available carbon atoms of the unit—V═W—X═Y— are substituted by a hydrogen atom, an alkyl, aralkyl or arylgroup, or R_(c) denotes a hydrogen atom or a C₁₋₈-alkyl group, aC₃₋₇-cycloalkyl, C₃₋₇-cycloalkyl-alkyl or aralkyl group which may besubstituted in each case by one or two alkyl groups or by an aryl group,an alkyl group which is substituted by a hydroxy, alkoxy, aryloxy,aralkoxy, alkylsulphenyl, alkylsulphinyl, alkylsulphonyl, arylsulphenyl,arylsulphinyl, arylsulphonyl, amino, alkylamino, dialkylamino,alkylcarbonylamino, N-alkyl-alkylcarbonylamino, alkylsulphonylamino,N-alkyl-alkylsulphonylamino, trifluoromethylsulphonylamino,N-alkyl-trifluoromethylsulphonylamino, carboxy, alkoxycarbonyl,aralkoxycarbonyl, aminocarbonyl, alkylaminocarbonyl,dialkylaminocarbonyl, cyano group, by a 2-, 3- or 4-pyridyl group, by analkyleneimino or (alkyleneimino)carbonyl group with in each case 4 to 7cyclic atoms in the alkyleneimino moiety, optionally substituted by 1 to4 alkyl groups, while in the abovementioned 6- to 7-memberedalkyleneimino groups a methylene group may be replaced in the 4-positionby an oxygen or sulphur atom, by an imino, N-alkyl-imino, N-aryl-imino,N-aralkyl-imino, N-arylcarbonyl-imino or N-alkylcarbonyl-imino group, aC₃₋₅-alkenyl group optionally substituted by an aryl group, while thevinyl moiety may not be attached to the nitrogen atom of the R_(c)NR_(d)group, a C₃₋₅-alkynyl group optionally substituted by an aryl group,while the ethynyl moiety may not be attached to the nitrogen atom of theR_(c)NR_(d) group, and R_(d) denotes a C₁₋₁₆-alkyl group which issubstituted by a group selected from the groups (a) to (n): (a) acarboxy, alkoxycarbonyl, aminocarbonyl, alkylaminocarbonyl,dialkylaminocarbonyl, hydroxy-C₂₋₄-alkylaminocarbonyl, cyano, hydroxy,alkoxy, aryloxy, aralkoxy, C₂₋₄-alkylenedioxy, alkylcarbonyloxy,arylcarbonyloxy, formylamino, alkylcarbonylamino, arylcarbonylamino,amino, alkylamino, dialkylamino, naphthylamino, aralkylamino,diaralkylamino or N-alkyl-aralkylamino group, (b) a phenylamino,N-alkyl-N-phenylamino, pyridylamino or N-alkyl-N-pyridylamino groupoptionally substituted in the aryl moiety by one or two fluorine,chlorine, bromine or iodine atoms or one or two nitro, trifluoromethyl,alkyl, hydroxy, alkoxy, amino, alkylamino, dialkylamino, carboxy,alkoxycarbonyl, aminocarbonyl, alkylaminocarbonyl, dialkylaminocarbonylor cyano groups, while the substituents may be identical or different,(c) an alkoxy group substituted by one, two or three aryl groups, (d) ahydroxy-C2-4-alkylaminocarbonyl, alkoxy-C2-4-alkylaminocarbonyl,amino-C2-4-alkylaminocarbonyl, alkylamino-C2-4-alkylaminocarbonyl,dialkylamino-C2-4-alkylaminocarbonyl, carboxyalkylaminocarbonyl,alkoxycarbonylalkylaminocarbonyl, aminocarbonylalkylaminocarbonyl,alkylaminocarbonylalkylaminocarbonyl,dialkylaminocarbonylalkylaminocarbonyl, arylaminocarbonyl,N-alkyl-arylaminocarbonyl, aralkylaminocarbonyl,N-alkyl-aralkylaminocarbonyl, (e) a group of formula —C(═NH)NH₂ or—NH—C(═NH)NH₂, which is optionally substituted by a cyano oralkoxycarbonyl group, (f) an (alkyleneimino)carbonyl group optionallysubstituted by 1 to 4 alkyl groups with in each case 4 to 7 cyclic atomsin the alkyleneimino moiety, while in a 6 or 7-membered alkyleneiminomoiety a methylene group in the 4-position may be replaced in each caseby an oxygen or sulphur atom, by a sulphinyl, sulphonyl, imino,N-alkyl-imino, N-alkylcarbonyl-imino, N-alkylsulphonyl-imino,N-aryl-imino or N-aralkyl-imino group, (g) a 4- to 7-memberedalkyleneimino group optionally substituted by 1 to 4 alkyl groups, whilein the abovementioned 6 or 7-membered alkyleneimino groups a methylenegroup in the 4-position may be replaced in each case by an oxygen orsulphur atom, by a sulphinyl, sulphonyl or R₁₀N group, where R₁₀ is ashereinbefore defined, and additionally in the abovementioned 5- to7-membered alkyleneimino groups in each case one or two methylene groupsadjacent to the nitrogen atoms may be replaced by a carbonyl group, (h)a 5- to 7-membered alkyleneimino group optionally substituted by 1 to 2alkyl groups which is substituted by a hydroxyalkyl, aminoalkyl,alkylaminoalkyl or dialkylaminoalkyl group, (i) an alkylsulphonylamino,N-alkyl-alkylsulphonylamino, arylcarbonylamino,N-alkyl-arylcarbonylamino, alkylcarbonylamino,N-alkyl-alkylcarbonylamino, arylsulphonylamino,N-alkyl-arylsulphonylamino, aralkylcarbonylamino,N-alkyl-aralkylcarbonylamino, alkoxyalkyl-carbonylamino,alkoxyalkyl-N-alkyl-carbonylamino, dialkylamino-alkylcarbonylamino,alkylamino-alkylcarbonylamino, amino-alkylcarbonylamino,aralkylsulphonylamino, N-alkyl-aralkylsulphonylamino,alkoxycarbonylamino, N-alkyl-alkoxycarbonylamino, aralkoxycarbonylaminoor N-alkyl-aralkoxycarbonylamino group, (j) a (R₉NR₈)—CO—NR₇ or(R₉NR₈)—SO2-NR₇ group, where R₇, R₈ and R₉ are as hereinbefore defined,(k) an alkylsulphenyl, alkylsulphinyl, alkylsulphonyl, arylsulphenyl,arylsulphinyl, arylsulphonyl, aralkylsulphenyl, aralkylsulphinyl oraralkylsulphonyl group, (l) a C₄₋₇-cycloalkyl group substituted by R₆and optionally additionally by 1 to 4 alkyl groups, where R₆ is ashereinbefore defined, (m) an C₅₋₇-cycloalkyl group optionallysubstituted by 1 to 4 alkyl groups wherein a methylene group is replacedby an oxygen or sulphur atom, by a sulphinyl, sulphonyl or NR₁₀ group,where R₁₀ is as hereinbefore defined, (n) a 4-piperidinyl-alkyl groupoptionally substituted by 1 to 4 alkyl groups, which is substituted inthe 1 position by R₁₀ and additionally in the 4-position by a hydroxygroup, where R₁₀ is as hereinbefore defined, and wherein additionallyhydrogen atoms in positions 2 and 6 of the piperidinyl structure aretogether replaced by a C₂₋₃-alkylene bridge, a methyl group substitutedby a 3-hydroxy-1,3-dihydro-indol-2-on-3-yl or2-aminocarbonyl-1,3-dihydro-isoindol-5-yl-group, a group of thestructure

substituted in the aryl moiety by a carboxy, alkoxycarbonyl,aminocarbonyl, alkylaminocarbonyl, dialkylaminocarbonyl, carboxyalkyl,alkoxycarbonylalkyl, aminocarbonylalkyl, alkylaminocarbonylalkyl ordialkylaminocarbonylalkyl group and optionally additionally substitutedin the alkylene moiety by 1 or 2 alkyl groups wherein x and y, which maybe identical or different, independently of one another represent thenumber 0, 1 or 2, but x and y together must yield at least the number 2,a C₃₋₈-alkyl group substituted by a hydroxy group and additionally by anamino, alkylamino, dialkylamino, hydroxy, alkoxy, 1-pyrrolidinyl,1-piperidinyl or morpholino group, a C₂₋₈-alkyl group substituted by acarboxy group and additionally by an amino, hydroxy, aminocarbonyl orbenzyloxycarbonylamino group, a C₂₋₄-alkyl group which is substituted bya C₂₋₄-alkylsulphenyl or C₂₋₄-alkoxy group, which is substituted in theo-position by an amino, hydroxy or alkoxy group, a C₂₋₄-alkyl groupwhich is substituted by a C₂₋₄-alkoxy-C₂₋₄-alkoxy group, which issubstituted in the o-position by an amino or hydroxy group, acyclopropyl group which is substituted by a carboxy, alkoxycarbonyl,aminocarbonyl, alkylaminocarbonyl or dialkylaminocarbonyl group or by an(alkyleneimino)carbonyl group optionally substituted by 1 to 4 alkylgroups with 4 to 7 cyclic atoms in the alkyleneimino moiety in eachcase, while in the abovementioned 6 or 7-membered alkyleneimino moietiesa methylene group in the 4-position may be replaced in each case by anoxygen or sulphur atom, by a sulphinyl, sulphonyl, imino, N-alkyl-imino,N-alkylcarbonyl-imino, N-alkylsulphonyl-imino, N-aryl-imino orN-aralkyl-imino group, a C₄₋₇-cycloalkyl group optionally substituted by1 to 4 alkyl groups, which is additionally substituted by R₆, which isas hereinbefore defined, a C₅₋₇-cycloalkyl group optionally substitutedby 1 to 2 alkyl groups which is additionally substituted by aN,N-dialkyl-N-oxido-amino group, a C₄₋₇-cycloalkyl group optionallysubstituted by 1 to 4 alkyl groups which may additionally be substitutedby R₆, while in the cycloalkyl moiety a methylene group is replaced byan oxygen or sulphur atom, by a sulphinyl, sulphonyl,N-alkyl-N-oxido-imino or R₁₀N group, where R₆ and R₁₀ are ashereinbefore defined, a C₅-C₇-cycloalkyl or C₅-C₇-cycloalkylalkyl groupoptionally substituted by 1 to 4 alkyl groups, wherein in each case amethylene group in the cycloalkyl moiety is replaced by a carbonylgroup, a cyclopentyl or cyclopentylalkyl group optionally substituted by1 to 4 alkyl groups, wherein in each case two hydrogen atoms in thecyclopentyl moiety are replaced by a straight-chain alkylene bridge,this bridge containing 2 to 6 carbon atoms, if the two hydrogen atomsare located on the same carbon atom, or 1 to 5 carbon atoms, if the twohydrogen atoms are located on adjacent carbon atoms, or 2 to 4 carbonatoms if the two hydrogen atoms are located on carbon atoms separated bya carbon atom, while the abovementioned rings are additionallysubstituted by the group R6, which is as hereinbefore defined, acyclohexyl, cyclohexylalkyl, cycloheptyl or cycloheptylalkyl groupoptionally substituted by 1 to 4 alkyl groups, wherein two hydrogenatoms in the cycloalkyl moiety are replaced by a straight-chain alkylenebridge in each case, this bridge containing 2 to 6 carbon atoms if thetwo hydrogen atoms are located on the same carbon atom, or 1 to 5 carbonatoms if the two hydrogen atoms are located on adjacent carbon atoms, or1 to 4 carbon atoms if the two hydrogen atoms are located on carbonatoms separated by a carbon atom, or 1 to 3 carbon atoms if the twohydrogen atoms are located on carbon atoms separated by two carbonatoms, while the abovementioned rings are additionally substituted bythe group R₆, which is as hereinbefore defined, an alkyl groupsubstituted by a 3-hydroxy-1,3-dihydro-indol-2-on-3-yl or2-aminocarbonyl-1,3-dihydro-isoindol-5-yl group, a C₁₋₁₀-alkyl groupsubstituted by an aryl group, while the abovementioned aryl moiety issubstituted by an alkoxycarbonyl, carboxy, carboxyalkyl, aminosulphonyl,trifluoromethoxy, cyano, aminoalkyl, amino, alkylamino, dialkylamino,nitro, 2H-pyridazin-3-on-6-yl, hydroxyphenyl, hydroxyalkyl, hydroxy oralkoxy group, an aralkyl group which is substituted in the aryl moietyby a hydroxy or alkoxy group and additionally by a carboxy,alkoxycarbonyl, hydroxy or alkoxy group, a C₁₋₁₀-alkyl group substitutedby a pyrrolyl, imidazolyl, pyrazolyl, pyridyl, pyrimidinyl, pyrazinyl,indolyl or benzimidazolyl group, while the abovementioned heteroarylmoieties on the available carbon atoms may additionally be substitutedin each case by one or two groups selected from fluorine, chlorine,bromine or iodine atoms, alkyl, alkoxycarbonyl, carboxy,trifluoromethyl, trifluoromethoxy, cyano, amino, alkylamino,dialkylamino, nitro, hydroxy or alkoxy groups, while the substituentsmay be identical or different, a C₁₋₁₀-alkyl group substituted by acarboxy, alkoxycarbonyl, aminocarbonyl, alkylaminocarbonyl,dialkylaminocarbonyl, aralkylaminocarbonyl, cyano, hydroxy, alkoxy,aryloxy, amino, alkylamino, dialkylamino, alkylcarbonylamino oralkoxycarbonylamino group, which is additionally substituted by one ortwo aryl groups or a pyrrolyl, imidazolyl, pyrazolyl, pyridyl,pyrimidinyl, pyrazinyl, indolyl or benzimidazolyl group, while theabovementioned aryl or heteroaryl moieties at the available carbon atomsmay additionally be substituted in each case by one or two groupsselected from fluorine, chlorine, bromine or iodine atoms, alkyl,alkoxycarbonyl, carboxy, trifluoromethyl, trifluoromethoxy, cyano,amino, alkylamino, dialkylamino, nitro, hydroxy or alkoxy groups, whilethe substituents may be identical or different, a C₁₋₆-alkyl groupsubstituted by an aryl group which is substituted in the aryl moiety bya hydroxy or amino group and additionally by two fluorine, chlorine,bromine or iodine atoms, while the substituents may be identical ordifferent, a C₂₋₆-alkyl group substituted by a carboxy or alkoxycarbonylgroup, which is additionally substituted by an amino, alkylamino,dialkylamino, alkylcarbonylamino, N-alkyl-alkylcarbonylamino,alkylsulphonylamino, N-alkyl-alkylsulphonylamino, arylcarbonylamino,N-alkyl-arylcarbonylamino, arylsulphonylamino,N-alkyl-arylsulphonylamino, aralkylcarbonylamino,N-alkyl-aralkylcarbonylamino, aralkylsulphonylamino,N-alkyl-aralkylsulphonylamino, alkoxycarbonylamino,N-alkyl-alkoxycarbonylamino, aralkoxycarbonylamino orN-alkyl-aralkoxycarbonylamino group, a 3-quinuclidinyl, 4-quinuclidinyl,2-quinuclidinyl-alkyl, 3-quinuclidinyl-alkyl or 4-quinuclidinyl-alkylgroup, or R_(c) denotes a hydrogen atom or an alkyl group and R_(d)denotes a hydroxy or alkoxy group, and R_(e) denotes a fluorine,chlorine, bromine or iodine atom, a cyano, nitro, alkyl, alkoxy,dialkylamino, alkylamino, alkylcarbonyl, alkylsulphenyl, alkylsulphinyl,alkylsulphonyl, alkoxyalkyl-alkylcarbonyl-N-alkyl-aminoalkyl,alkylcarbonyl-aminoalkyl, alkylsulphonyl-aminoalkyl, aminocarbonyl,alkylaminocarbonyl, dialkylaminocarbonyl, aminoalkyl, alkylaminoalkyl ordialkylaminoalkyl group, a methyl, methylsulphenyl or methoxy groupsubstituted by 1 to 3 fluorine atoms, a C₂₋₄-alkyl, C₂₋₄-alkylsulphenylor C₂₋₄-alkoxy group substituted by 1 to 5 fluorine atoms, anC₃₋₆-cycloalkyl-C₁₋₃-alkyl group optionally substituted by 1-6 fluorineatoms, a C₂₋₅-alkenyl or C₃₋₅-alkenyloxy group, while the vinyl moietymay not be attached to the oxygen atom, a C₂₋₆-alkynyl orC₃₋₆-alkynyloxy group, while the ethynyl moiety may not be attached tothe oxygen atom, an alkyleneimino or alkyleneimino-alkyl group with ineach case 4 to 7 cyclic atoms in the alkyleneimino moiety optionallysubstituted by 1 to 4 alkyl groups, while in a 6- or 7-memberedalkyleneimino moiety a methylene group in the 4-position may be replacedin each case by an oxygen or sulphur atom, by a sulphinyl, sulphonyl,imino, N-alkyl-imino, N-alkylcarbonyl-imino, N-alkylsulphonyl-imino,N-aryl-imino or N-aralkyl-imino group, or a tautomer, racemate,enantiomer, diastereomer or mixture thereof, or a pharmacologicallyacceptable acid addition salt thereof, wherein, unless otherwise stated,by the aryl moieties set forth above, either alone or as part of anothergroup, is meant a phenyl group, wherein one or two carbon atoms may bereplaced by a nitrogen atom in each case, wherein the abovementionedaryl moieties in each case may be monosubstituted by R₁₁, mono, di ortrisubstituted by R₁₂ or monosubstituted by R₁₁, and additionally mono-or disubstituted by R₁₂, while the substituents may be identical ordifferent, and R₁₁, denotes a cyano, carboxy, aminocarbonyl,alkylaminocarbonyl, dialkylaminocarbonyl, alkoxycarbonyl, alkylcarbonyl,alkylsulphenyl, alkylsulphinyl, alkylsulphonyl, alkylsulphonyloxy,perfluoroalkyl, perfluoroalkoxy, nitro, amino, alkylcarbonylamino,N-alkyl-alkylcarbonylamino, alkylamino, dialkylamino,hydroxy-C2-4-alkylamino, N-alkyl-(hydroxy-C2-4-alkyl)amino,bis-(hydroxy-C2-4-alkyl)amino, phenylalkylcarbonylamino,phenylcarbonylamino, alkylsulphonylamino, phenylalkylsulphonylamino,phenylsulphonylamino, N-alkyl-phenylalkylcarbonylamino,N-alkyl-phenylcarbonylamino, N-alkyl-alkylsulphonylamino,N-alkyl-phenylalkylsulphonylamino, N-alkyl-phenylsulphonylamino,aminosulphonyl, alkylaminosulphonyl, dialkylaminosulphonyl,(R₉NR₈)—CO—NR₇ or (R₉NR₈)—SO2-NR₇ group, where R₇, R₈ and R₉ are ashereinbefore defined, a 5- to 7-membered alkyleneimino group optionallysubstituted by 1 to 4 alkyl groups or a hydroxyalkyl group, while in theabovementioned 6- to 7-membered alkyleneimino groups a methylene groupin the 4-position may be replaced in each case by an oxygen atom or anR₁₀N group, where R₁₀ is as hereinbefore defined, a 5- to 7-memberedalkyleneimino group optionally substituted by 1 to 4 alkyl groups or ahydroxyalkyl group, while in each case one or two methylene groupsadjacent to the nitrogen atom is replaced by a carbonyl group in eachcase, and R₁₂ denotes an alkyl, hydroxy or alkoxy group, a fluorine,chlorine, bromine or iodine atom, while two groups R₁₂, if they arebound to adjacent carbon atoms, may also denote an alkylene group with 3to 6 carbon atoms, a 1,3-butadiene-1,4-diylene group or a methylenedioxygroup, and, unless stated to the contrary, the abovementioned alkyl,alkylene and alkoxy moieties each contain 1 to 4 carbon atoms, wherein,unless otherwise stated, each carbon atom in the abovementioned alkyl,alkylene or cycloalkylene moieties, which is bound to a nitrogen, oxygenor sulphur atom, cannot be bound to any other halogen, nitrogen, oxygenor sulphur atom.
 2. A compound of formula I according to claim 1,wherein R_(a) denotes a hydrogen atom or an alkyl group, R_(b) denotesan aralkyl group which may be substituted in the aryl moiety by acarboxy, alkoxycarbonyl, aminocarbonyl, alkylaminocarbonyl,dialkylaminocarbonyl, amino, alkylamino, dialkylamino, cyano,trifluoromethyl or nitro group or one or two fluorine, chlorine, bromineor iodine atoms or one or two hydroxy, alkyl or alkoxy groups, while thesubstituents may be identical or different, or by a 5- to 7-memberedalkyleneimino group, while in each case one or two methylene groupsadjacent to the nitrogen atom may be replaced in each case by a carbonylgroup or in the abovementioned 6- to 7-membered alkyleneimino groups amethylene group in the 4-position may be replaced by an oxygen atom, byan imino, N-aryl-imino or N-alkyl-imino group, and wherein the alkylenemoiety of the abovementioned aralkyl groups may be substituted by one ortwo alkyl groups, or a phenyl group optionally substituted by the groupsR₁ to R₃, while R₁ denotes a fluorine, chlorine, bromine or iodine atom,a C₁₋₂-alkyl or hydroxy group, a C₃₋₆-cycloalkyl or C₅₋₆-cycloalkoxygroup, a C₂₋₅-alkenyl group, a C₂₋₅-alkynyl group, an aryl, aryloxy,aralkyl, aralkoxy, alkylsulphenyl, alkylsulphinyl, alkylsulphonyl,alkylsulphonyloxy, trifluoromethylsulphenyl, trifluoromethylsulphonyl,arylsulphenyl, arylsulphinyl, arylsulphonyl, aralkylsulphenyl,aralkylsulphinyl or aralkylsulphonyl group, a methyl or methoxy groupsubstituted by 1 to 3 fluorine atoms, a C₂₋₄-alkyl or C₂₋₄-alkoxy groupsubstituted by 1 to 5 fluorine atoms, a nitro, amino, alkylamino,dialkylamino, C₃₋₆-cycloalkylamino, N-alkyl-C₃₋₆-cycloalkylamino,arylamino, N-alkyl-arylamino, aralkylamino or N-alkyl-aralkylaminogroup, a 5- to 7-membered alkyleneimino group, while in each case one ortwo methylene groups adjacent to the nitrogen atom may be replaced ineach case by a carbonyl group or in the abovementioned 6- to 7-memberedalkyleneimino groups a methylene group in the 4-position may be replacedby an oxygen atom, by an imino, N-aryl-imino or N-alkyl-imino group andthe alkyleneimino groups may additionally be substituted by 1-2 methylgroups, an (alkyleneimino)carbonyl or (alkyleneimino)sulphonyl groupwith in each case 5 to 7 cyclic atoms in the alkyleneimino moiety, whilein the abovementioned 6-to 7-membered alkyleneimino moieties a methylenegroup in the 4-position may be replaced in each case by an oxygen atom,by an imino, N-aryl-imino or N-alkyl-imino group, an alkylcarbonylamino,N-alkyl-alkylcarbonylamino, alkyl-sulphonylamino,N-alkyl-alkylsulphonylamino, arylcarbonylamino,N-alkyl-arylcarbonylamino, arylsulphonylamino,N-alkyl-arylsulphonylamino, aralkylcarbonylamino,N-alkyl-aralkylcarbonylamino, aralkylsulphonylamino,N-alkyl-aralkylsulphonylamino, trifluoromethylsulphonylamino,N-alkyl-trifluoromethylsulphonylamino, alkylcarbonyl, arylcarbonyl,aralkylcarbonyl, carboxy, alkoxycarbonyl, aminocarbonyl,alkylaminocarbonyl, dialkylaminocarbonyl, arylaminocarbonyl,N-alkyl-arylaminocarbonyl, aralkylaminocarbonyl,N-alkyl-aralkylaminocarbonyl, N-hydroxy-aminocarbonyl,N-hydroxy-alkylaminocarbonyl, N-alkoxy-aminocarbonyl,N-alkoxy-alkylaminocarbonyl, cyano, azido, N-cyano-amino orN-cyano-alkylamino group, a sulpho, aminosulphonyl, alkylaminosulphonyl,dialkylaminosulphonyl, arylaminosulphonyl, pyridylaminosulphonyl,N-alkyl-arylaminosulphonyl, aralkylaminosulphonyl orN-alkyl-aralkylaminosulphonyl group, or a C₁₋₂ alkyl group substitutedby R₄, wherein R₄ denotes a hydroxy, alkoxy, aryloxy, amino, alkylamino,fluoroalkylamino, dialkylamino, alkylsulphenyl, alkylsulphinyl,alkylsulphonyl, arylsulphenyl, arylsulphinyl, arylsulphonyl, carboxy,alkoxycarbonyl, aminocarbonyl, alkylaminocarbonyl, dialkylaminocarbonylor cyano group, a 5- to 7-membered alkyleneimino group optionallysubstituted by one or two alkyl groups, while in the abovementioned 6-to 7-membered alkyleneimino groups a methylene group in the 4-positionmay be replaced by an oxygen or sulphur atom, by an imino,N-alkyl-imino, N-alkylcarbonyl-imino, N-alkylsulphonyl-imino,N-arylcarbonyl-imino, N-arylsulphonyl-imino, N-aryl-imino orN-aralkyl-imino group, or may be substituted by a hydroxy, alkoxy,aminocarbonyl, alkylaminocarbonyl, dialkylaminocarbonyl, amino,alkylamino- and dialkylamino group, or an (alkyleneimino)carbonyl groupwith in each case 5 to 7 cyclic atoms in the alkyleneimino moietyoptionally substituted by one or two alkyl groups, while in theabovementioned 6- to 7-membered alkyleneimino moieties a methylene groupin the 4-position may be replaced in each case by an oxygen or sulphuratom, by an imino, N-alkyl-imino or N-alkylcarbonyl-imino group, or  agroup of formula

 wherein h and k, which may be identical or different, represent thenumbers 1 to 2 or h denotes the number 0 and k denotes the number 2 or3, while additionally the above benzo portion may be substituted by afluorine, chlorine, bromine or iodine atom or by an alkyl,trifluoromethyl, hydroxy, alkoxy, carboxy or cyano group and the abovesaturated cyclic imino moiety may be substituted by 1 or 2 alkyl groups,R₂ denotes a fluorine, chlorine or bromine atom, a C₁₋₂ alkyl,trifluoromethyl, hydroxy, amino, alkylamino, dialkylamino,alkylcarbonylamino, N-alkyl-alkylcarbonylamino, alkylsulphonylamino,N-alkyl-alkylsulphonylamino, trifluoromethylsulphonylamino,N-alkyl-trifluoromethylsulphonylamino or cyano group, and R₃ denotes afluorine, chlorine or bromine atom, a C₁₋₂ alkyl, trifluoromethyl oralkoxy group, a group of the structure

 wherein the point of attachment may be a carbon or a nitrogen atom andup to three carbon atoms may be replaced by a nitrogen atom and the ringmay be substituted, via each of the atoms, by one or two alkyl, aryl oraralkyl groups, or a sulpho, aminosulphonyl, alkylaminosulphonyl,dialkylaminosulphonyl, arylaminosulphonyl, pyridylaminosulphonyl,N-alkyl-arylaminosulphonyl, aralkylaminosulphonyl orN-alkyl-aralkylaminosulphonyl group R₂ together with R₃, if they arebound to adjacent carbon atoms, denote a methylenedioxy group optionallysubstituted by one or two alkyl groups, or an n-C₃₋₅-alkylene groupoptionally substituted by one or two alkyl groups wherein a methylenegroup may be replaced by an oxygen atom, by an imino, N-alkyl-imino orN-aralkyl-imino group, or a 1,3-butadiene-1,4-diylene group optionallysubstituted by a fluorine, chlorine or bromine atom, by a hydroxy,alkyl, alkoxy, trifluoromethyl, carboxy or cyano group or a group offormula —NH—C(═O)—(CH₂) or —NH—C(═O)—(CH₂)₂, which may additionally besubstituted in the alkylene moiety by 1 or 2 alkyl groups, or a group offormula —NH—N═N, —NH—N═CH, —NH—CH═N—, —O—CH═N, —S—CH═N, —NH—CH═CH— andthe tautomers thereof, while each hydrogen atom may be substituted by analkyl, aryl or aralkyl group, or a group of formula—(CH₂)_(m)—NR₅—(CH₂)_(n)—, wherein m and n which may be identical ordifferent in each case represent 1 or 2, and R₅ denotes hydrogen, C₁₋₆alkyl or C₁₋₆ fluoroalkyl, or R_(a) together with R₁, if R1 is in theo-position to the nitrogen atom substituted by R_(a), also denote ann-C₂₋₃-alkylene group optionally substituted by one or two alkyl groups,and R_(c)NR_(d) represents a 4- to 7-membered alkyleneimino groupoptionally substituted by 1 to 2 alkyl or aryl groups which isadditionally substituted by the group R₆, where R₆ denotes a carboxy,alkoxycarbonyl, aminoalkyl, aminocarbonyl, alkylaminocarbonyl,dialkylaminocarbonyl, cyano, hydroxy, alkoxy, aryloxy, aralkoxy,alkylcarbonyloxy, arylcarbonyloxy, amino, alkylamino,hydroxy-C₂₋₄-alkylamino, dialkylamino, cyanamino, formylamino,alkylsulphenyl, alkylsulphinyl, alkylsulphonyl, arylsulphenyl,arylsulphinyl, arylsulphonyl, aralkylsulphenyl, aralkylsulphinyl oraralkylsulphonyl group, an alkylcarbonylamino,N-alkyl-alkylcarbonylamino, alkylsulphonylamino,N-alkyl-alkylsulphonylamino, arylcarbonylamino,N-alkyl-arylcarbonylamino, arylsulphonylamino,N-alkyl-arylsulphonylamino, aralkylcarbonylamino,N-alkyl-aralkylcarbonylamino, aralkylsulphonylamino,N-alkyl-aralkylsulphonylamino, alkoxycarbonylamino,N-alkyl-alkoxycarbonylamino, alkoxycarbonylalkylamino,N-(alkyl)-N-(alkoxycarbonylalkyl)-amino, aralkoxycarbonylamino orN-alkyl-aralkoxycarbonylamino group, a (NR₈R₉)CONR₇ group wherein R₇ andR₈ in each case denote a hydrogen atom or an alkyl group and R9 denotesa hydrogen atom or an alkyl, aryl or pyridyl group, while the groups R₇,R₈ and R₉ may be identical or different, or R₇ and R₈ together denote an-C₂₋₄-alkylene group and R₉ is a hydrogen atom or an alkyl, aryl orpyridyl group, an alkyleneimino group with 5 to 7 cyclic atoms in thealkyleneimino moiety optionally substituted by 1 to 2 alkyl groups,while in the abovementioned 6- to 7-membered alkyleneimino moieties amethylene group in the 4-position of the alkyleneimino moiety may bereplaced in each case by an oxygen or sulphur atom, by a carbonyl,sulphinyl, sulphonyl, imino, N-alkylimino, N-alkylcarbonyl-imino,N-alkylsulphonyl-imino, N-arylimino or N-aralkyl-imino group, an(alkyleneimino)carbonyl group with in each case 4 to 7 cyclic atoms inthe alkyleneimino moiety optionally substituted by 1 to 2 alkyl groups,while in the abovementioned 6- to 7-membered alkyleneimino moieties amethylene group in the 4-position may be replaced in each case by anoxygen or sulphur atom, by a sulphinyl, sulphonyl, imino, N-alkyl-imino,N-alkylcarbonyl-imino, N-alkylsulphonyl-imino, N-aryl-imino orN-aralkyl-imino group, a 4- to 7-membered alkyleneimino groupsubstituted by a hydroxy, alkoxy, amino, alkylamino, dialkylamino,alkylcarbonylamino, N-alkyl-alkylcarbonylamino, alkylsulphonylamino,N-alkyl-alkylsulphonylamino, hydroxyalkyl, carboxy, alkoxycarbonyl,aminocarbonyl, alkylaminocarbonyl or dialkylaminocarbonyl group, analkyl group substituted by a carboxy, alkoxycarbonyl, aminocarbonyl,alkylaminocarbonyl, dialkylaminocarbonyl, cyano, hydroxy, alkoxy,aryloxy, amino, alkylamino, dialkylamino, alkylcarbonylamino,N-alkyl-alkylcarbonylamino, alkoxycarbonylamino,N-alkyl-alkoxycarbonylamino, alkylsulphonylamino,N-alkyl-alkylsulphonylamino, arylcarbonylamino,N-alkyl-arylcarbonylamino, arylsulphonylamino,N-alkyl-arylsulphonylamino, dialkylaminocarbonylalkylamino,N-(alkyl)-N-(dialkylaminocarbonylalkyl)-amino, dialkylaminoalkoxy,alkylsulphenyl, alkylsulphinyl, alkylsulphonyl, arylsulphenyl,arylsulphinyl or arylsulphonyl group, an (alkyleneimino)alkyl group within each case 4 to 7 cyclic atoms in the alkyleneimino moiety optionallysubstituted by 1 to 2 alkyl groups, while in the abovementioned 6- to7-membered alkyleneimino moieties a methylene group in the 4-positionmay be replaced in each case by an oxygen or sulphur atom, by asulphinyl, sulphonyl, imino, N-alkyl-imino or N-alkylcarbonyl-iminogroup, an (alkyleneimino)carbonylalkyl group with in each case 4 to 7cyclic atoms in the alkyleneimino moiety optionally substituted by 1 to2 alkyl groups, while in the abovementioned 6- to 7-memberedalkyleneimino moieties a methylene group in the 4-position may bereplaced in each case by an oxygen or sulphur atom, by a sulphinyl,sulphonyl, imino or N-alkyl-imino group, a (carboxyalkyl)oxy,(alkoxycarbonylalkyl)oxy, (aminocarbonylalkyl)oxy,(alkylaminocarbonylalkyl)oxy or (dialkylaminocarbonylalkyl)oxy group, a3,4-dihydro-1H-quinazolin-2-on-3-yl or 1H-benzimidazol-2-on-1-yl groupoptionally substituted in the aryl moiety by one or two fluorine,chlorine, bromine or iodine atoms or one or two nitro, alkyl, alkoxy orcyano groups in each case, while the substituents may be identical ordifferent, or R_(c)NR_(d) denotes a 6- to 7-membered alkyleneimino groupoptionally substituted by 1 to 2 alkyl groups or by an aryl group, whichmay additionally be substituted by the group R₆, while in theabovementioned alkyleneimino groups a methylene group in the 4-positionis replaced in each case by an oxygen or sulphur atom, by a carbonyl,sulphinyl, sulphonyl or R₁₀N group, where R₁₀ denotes a hydrogen atom,an alkyl, hydroxy-C₂₋₄-alkyl, amino-C₂₋₄-alkyl, alkylamino-C₂₋₄-alkyl,dialkylamino-C₂₋₄-alkyl, (hydroxy-C₂₋₄-alkoxy)-C₂₋₄-alkyl,aminocarbonylalkyl, alkylaminocarbonylalkyl, dialkylaminocarbonylalkyl,aryl, formyl, alkylcarbonyl, alkylsulphonyl, arylcarbonyl,arylsulphonyl, aralkylcarbonyl, aralkylsulphonyl, alkoxycarbonyl,aralkoxycarbonyl, cyano, aminocarbonyl, alkylaminocarbonyl ordialkylaminocarbonyl group, an amino-alkylcarbonyl,alkylamino-alkylcarbonyl, dialkylamino-alkylcarbonyl-group, a methylgroup substituted by one or two aryl groups, while the aryl moieties maybe substituted independently of one another by one or two fluorine,chlorine, bromine or iodine atoms or one or two nitro, alkyl, hydroxy oralkoxy groups in each case, while the substituents may be identical ordifferent, a 2-, 3- or 4-pyridyl group, a 2-, 4- or 5-pyrimidyl group, aphenyl group optionally substituted by one or two fluorine, chlorine,bromine or iodine atoms or one or two nitro, trifluoromethyl, alkyl,hydroxy, alkoxy, amino, alkylamino, dialkylamino, carboxy,alkoxycarbonyl, aminocarbonyl, alkylaminocarbonyl, dialkylaminocarbonylor cyano groups, while the substituents may be identical or different, a8-methyl-8-aza-bicyclo[3.2.1]oct-3-yl group, or an(alkyleneimino)carbonyl or (alkyleneimino)carbonylalkyl group with ineach case 5 to 7 cyclic atoms in the alkyleneimino moiety, while in theabove-mentioned 6- to 7-membered alkyleneimino moieties a methylenegroup in the 4-position may be replaced in each case by an oxygen orsulphur atom, by a sulphinyl, sulphonyl, imino, N-alkyl-imino,N-alkylcarbonyl-imino or N-aralkyl-imino group, or R_(c)NR_(d) denotes a3-thiazolidinyl group substituted in the 4-position by a carboxy,alkoxycarbonyl, aminocarbonyl, alkylaminocarbonyl ordialkylaminocarbonyl group, or R_(c)NR_(d) denotes a 1-piperidinyl groupoptionally substituted by 1 to 2 alkyl groups, wherein two hydrogenatoms on the carbon skeleton are replaced by a straight-chain alkylenebridge, this bridge containing 2 to 6 carbon atoms, if the two hydrogenatoms are located on the same carbon atom, or 1 to 5 carbon atoms if thetwo hydrogen atoms are located on adjacent carbon atoms, or 1 to 4carbon atoms if the two hydrogen atoms are located on carbon atoms whichare separated by one atom, or 1 to 3 carbon atoms if the two hydrogenatoms are located on carbon atoms which are separated by two atoms,while the abovementioned 1-piperidinyl groups are additionallysubstituted by the group R₆, which is as hereinbefore defined, a1-pyrrolidinyl or 1-piperidinyl group optionally substituted by 1 to 2alkyl groups, wherein the two hydrogen atoms of a methylene group arereplaced by a straight-chain C3-6-alkylene bridge, while in each case amethylene group in the C₃₋₆-alkylene bridge is replaced by a R₁₀N group,where R₁₀ is as hereinbefore defined, while the bicyclic ring thusformed is optionally additionally substituted by a hydroxy, alkoxy,amino, alkylamino, dialkylamino, cyano, alkylcarbonylamino,alkylsulphonylamino, alkoxycarbonylamino, arylcarbonyl, carboxy,alkoxycarbonyl, aminocarbonyl, alkylaminocarbonyl ordialkylaminocarbonyl group, a group of the structure

optionally substituted by 1 or 2 alkyl groups in the alkylene moietieswherein p and q, which may be identical or different, independently ofone another denote the number 1 or 2, and the unit —V═W—X═Y— denotes oneof the groups (a) or (b): —N═C—C═C— (a), —C═N—C═C— (b),

while one of the available carbon atoms of the groups (a) or (b) may besubstituted by a hydroxy, alkoxy, amino, alkylamino or dialkylaminogroup and the remaining available carbon atoms of the groups (a) or (b)are substituted by a hydrogen atom, an alkyl or aryl group, or —V═W—taken together represent an oxygen or sulphur atom or an imino,N-alkyl-imino or N-aryl-imino group and —X═Y— represents one of thegroups —N═C or —C═N—, or, if n and m are not the same, —X═Y— takentogether represent an oxygen or sulphur atom or an imino, N-alkyl-iminoor N-aryl-imino group and —V═W— represents one of the groups —N═C or—C═N—, or R_(c) represents a hydrogen atom, an aralkyl or a C₁₋₆-alkylgroup, an alkyl group which is substituted by a hydroxy, alkoxy,aryloxy, aralkoxy, amino, alkylamino, dialkylamino, alkylcarbonylamino,N-alkyl-alkylcarbonylamino, alkylsulphonylamino,N-alkyl-alkylsulphonylamino, trifluoromethylsulphonylamino,N-alkyl-trifluoromethylsulphonylamino, carboxy, alkoxycarbonyl,aminocarbonyl, alkylaminocarbonyl, dialkylaminocarbonyl, cyano or by a2-, 3- or 4-pyridyl group with the proviso that the hetero atoms areseparated from the nitrogen atom of the R_(c)NR_(d) group by two or morecarbon atoms, a C₃₋₅-alkenyl group, while the vinyl moiety may not beattached to the nitrogen atom of the R_(c)NR_(d) group, a C₃₋₅-alkynylgroup, while the ethynyl moiety may not be attached to the nitrogen atomof the R_(c)NR_(d) group, and R_(d) denotes a C₁₋₁₀-alkyl group which issubstituted by a group selected from the groups (a) to (n): (a) acarboxy, alkoxycarbonyl, aminocarbonyl, alkylaminocarbonyl,dialkylaminocarbonyl, cyano, hydroxy, alkoxy, aryloxy, aralkoxy,alkylcarbonylamino, amino, alkylamino, dialkylamino, naphthylamino,aralkylamino, diaralkylamino or N-alkyl-aralkylamino group, (b) aphenylamino or pyridylamino group optionally substituted in the arylmoiety by a fluorine, chlorine, bromine or iodine atom or a nitro,trifluoromethyl, alkyl, hydroxy, alkoxy, amino, alkylamino,dialkylamino, carboxy, alkoxycarbonyl, aminocarbonyl,alkylaminocarbonyl, dialkylaminocarbonyl or cyano group, (c) a methoxygroup substituted by one, two or three aryl groups, (d) acarboxyalkylaminocarbonyl, alkoxycarbonylalkylaminocarbonyl,amino-carbonylalkylaminocarbonyl, alkylaminocarbonylalkylaminocarbonyl,dialkylaminocarbonylalkylaminocarbonyl, arylaminocarbonyl,N-alkylarylaminocarbonyl, aralkylaminocarbonyl,N-alkyl-aralkylaminocarbonyl, (e) a group of formula-C(═NH)NH₂, (f) an(alkyleneimino)carbonyl group with in each case 5 to 7 cyclic atoms inthe alkyleneimino moiety optionally substituted by 1 to 2 alkyl groups,while in the abovementioned 6- to 7-membered alkyleneimino groups amethylene group in the 4-position may be replaced in each case by anoxygen or sulphur atom, by a sulphinyl, sulphonyl, imino, N-alkyl-imino,N-alkylcarbonyl-imino, N-alkylsulphonyl-imino, N-aryl-imino orN-aralkyl-imino group, (g) a 4- to 7-membered alkyleneimino groupoptionally substituted by 1 to 2 alkyl groups, while in theabovementioned 6- to 7-membered alkyleneimino groups a methylene groupin the 4-position may be replaced in each case by an oxygen or sulphuratom, by a sulphinyl, sulphonyl or R₁₀N group, where R₁₀ is ashereinbefore defined, and additionally in the abovementioned 5- to7-membered alkyleneimino groups a methylene group adjacent to thenitrogen atoms may be replaced by a carbonyl group in each case, (h) a5- to 7-membered alkyleneimino group optionally substituted by 1 to 2alkyl groups which is substituted by a hydroxyalkyl, aminoalkyl,alkylaminoalkyl or dialkylaminoalkyl group, (i) an alkylsulphonylamino,N-alkyl-alkylsulphonylamino, arylcarbonylamino,N-alkyl-arylcarbonylamino, alkylcarbonylamino,N-alkyl-alkylcarbonylamino, alkoxy-alkylcarbonylamino,dialkylamino-alkylcarbonylamino, arylsulphonylamino,N-alkyl-arylsulphonylamino, aralkylcarbonylamino,N-alkylaralkylcarbonylamino, aralkylsulphonylamino,N-alkyl-aralkylsulphonylamino, alkoxycarbonylamino,N-alkyl-alkoxycarbonylamino, aralkoxycarbonylamino orN-alkyl-aralkoxycarbonylamino group, (j) a (R₉NR₈)—CO—NR₇ group, whereR₇, R₈ and R₉ are as hereinbefore defined, (k) a2-aza-bicyclo[2.2.1]hept-5-en-2-yl group, (l) an alkylsulphenyl,alkylsulphinyl, alkylsulphonyl, arylsulphenyl, arylsulphinyl orarylsulphonyl group, (m) a C₄₋₇-cycloalkyl group substituted by R₆ andoptionally additionally substituted by 1 to 2 alkyl groups, while R₆ isas hereinbefore defined, (n) a C₅₋₇-cycloalkyl group optionallysubstituted by 1 to 4 alkyl groups wherein a methylene group is replacedby an oxygen atom or a NR₁₀ group, while R₁₀ is as hereinbefore defined,a 4-piperidinyl-methyl group which is substituted in the 1-position byR₁₀ and additionally in the 4-position by a hydroxy group, where R₁₀ isas hereinbefore defined, and wherein additionally a hydrogen atom ineach of positions 2 and 6 of the piperidinyl structure are togetherreplaced by a C₂₋₃-alkylene bridge, a methyl group substituted by a3-hydroxy-1,3-dihydro-indol-2-on-3-yl or2-aminocarbonyl-1,3-dihydro-isoindol-5-yl group, a group of thestructure

substituted in the aryl moiety by a carboxy or carboxyalkyl group andoptionally additionally substituted in the alkylene moiety by 1 or 2alkyl groups while p and q, which may be identical or different, denotethe number 0, 1 or 2, but p and q together must at least yield thenumber 2, a C₃₋₆-alkyl group substituted by a hydroxy group andadditionally substituted by an amino, alkylamino, dialkylamino, hydroxy,alkoxy, 1-pyrrolidinyl, 1-piperidinyl or morpholino group, a C₂₋₆-alkylgroup substituted by a carboxy group and additionally substituted by anamino, hydroxy, aminocarbonyl or benzyloxycarbonylamino group, aC₂₋₄-alkyl group which is substituted by a C₂₋₄-alkylsulphenyl group,which is substituted in the ω-position by a ω-amino group, a C₂₋₄-alkylgroup which is substituted by a C₂₋₄-alkoxy group, which is substitutedin the ω-position by an amino, hydroxy or alkoxy group, a C₂₋₄-alkylgroup which is substituted by a C₂₋₄-alkoxy-C₂₋₄-alkoxy group, which issubstituted in the ω-position by an amino or hydroxy group, aC₄₋₇-cycloalkyl group optionally substituted by 1 to 2 alkyl groups,which is additionally substituted by R₆, which is as hereinbeforedefined, a C₄₋₇-cycloalkyl group optionally substituted by 1 to 2 alkylgroups, which may additionally be substituted by R₆, while in thecycloalkyl moiety a methylene group is replaced by an oxygen or sulphuratom, by a sulphinyl, sulphonyl or R₁₀N group, while R₆ and R₁₀ are ashereinbefore defined, a methyl group substituted by a3-hydroxy-1,3-dihydro-indol-2-on-3-yl or2-aminocarbonyl-1,3-dihydro-isoindol-5-yl group, a C₁₋₆-alkyl groupsubstituted by an aryl group, while the abovementioned aryl moiety issubstituted by an alkoxycarbonyl, carboxy, carboxyalkyl, aminosulphonyl,trifluoromethoxy, cyano, aminoalkyl, amino, alkylamino, dialkylamino,nitro, 2H-pyridazin-3-on-6-yl, hydroxyphenyl, hydroxyalkyl, hydroxy oralkoxy group, an aralkyl group which is substituted in the aryl moietyby an alkoxy or hydroxy group and additionally by an alkoxycarbonyl,carboxy, alkoxy or hydroxy group, a C₁₋₆-alkyl group substituted by a2-pyridyl, 3-pyridyl, 4-pyridyl, 2-pyrazinyl-, 1H-pyrrol-2-yl,1H-pyrazol-4-yl-, 1H-pyrazol-5-yl, 1H-imidazol-1-yl, 1H-imidazol-4-yl,1H-indol-3-yl or 1H-benzimidazol-2-yl group, while the abovementionedheteroaryl moieties at the available carbon atoms may additionally besubstituted in each case by one or two groups selected from fluorine,chlorine, bromine or iodine atoms, alkyl, alkoxycarbonyl, carboxy,trifluoromethyl, trifluoromethoxy, cyano, amino, alkylamino,dialkylamino, nitro, hydroxy or alkoxy groups, while the substituentsmay be identical or different, a C₁₋₆-alkyl group substituted by acarboxy, alkoxycarbonyl, aminocarbonyl, alkylaminocarbonyl,dialkylaminocarbonyl, aralkylaminocarbonyl, cyano, hydroxy, alkoxy,aryloxy, amino, alkylamino, dialkylamino, alkylcarbonylamino oralkoxycarbonylamino group, which is additionally substituted by one ortwo aryl groups or a heteroaryl group, while the heteroaryl groupdenotes a 2-pyridyl, 3-pyridyl, 4-pyridyl, 2-pyrazinyl-, 1H-pyrrol-2-yl,1H-pyrazol-4-yl-, 1H-pyrazol-5-yl, 1H-imidazol-1-yl, 1H-imidazol-4-yl,1H-indol-3-yl or 1H-benzimidazol-2-yl group, while the above-mentionedaryl or heteroaryl moieties at the available carbon atoms mayadditionally be substituted in each case by one or two groups selectedfrom fluorine, chlorine, bromine or iodine atoms, alkyl, alkoxycarbonyl,carboxy, trifluoromethyl, trifluoromethoxy, cyano, amino, alkylamino,dialkylamino, nitro, hydroxy or alkoxy groups, while the substituentsmay be identical or different, a C₁₋₆-alkyl group substituted by an arylgroup which is substituted in the aryl moiety by a hydroxy or aminogroup and is additionally substituted by two fluorine, chlorine, bromineor iodine atoms, while the substituents may be identical or different, aC₂₋₆-alkyl group substituted by a carboxy or alkoxycarbonyl group whichis additionally substituted by an amino, alkylamino, dialkylamino,alkylcarbonylamino, arylcarbonylamino, arylsulphonylamino,alkoxycarbonylamino or aralkoxycarbonylamino group, a 3-quinuclidinyl or4-quinuclidinyl group, and R_(e) denotes a fluorine, chlorine, bromineor iodine atom, an alkyl, alkoxy, dialkylamino, allyl, ethynyl,methylsulphenyl, methylsulphonyl, alkoxymethyl, nitro, cyano ordialkylaminomethyl group, a methyl, ethyl, methylsulphenyl or methoxygroup substituted by 1 to 3 fluorine atoms, an alkyleneimino oralkyleneimino-methyl group with 4 to 7 cyclic atoms in the alkyleneiminomoiety in each case, while in a 6 or 7-membered alkyleneimino moiety amethylene group in the 4-position may be replaced in each case by anoxygen or sulphur atom, by an N-alkyl-imino, N-alkylcarbonyl-imino,N-alkylsulphonyl-imino, N-aryl-imino or N-aralkyl-imino group, while,unless otherwise specified, the abovementioned alkyl, alkylene andalkoxy moieties in each case contain 1 to 4 carbon atoms, or a tautomer,racemate, enantiomer, diastereomer or mixture thereof, or apharmacologically acceptable acid addition salt thereof, wherein, unlessotherwise stated, each carbon atom in the abovementioned alkyl, alkyleneor cycloalkylene moieties which is bound to a nitrogen, oxygen orsulphur atom, cannot be bound to any other halogen, nitrogen, oxygen orsulphur atom.
 3. A compound of formula I according to claim 2, whereinR_(a) denotes a hydrogen atom or a methyl group, R_(b) denotes anaphthyl group optionally substituted by a fluorine, chlorine or bromineatom or by a carboxy, C₁₋₂ alkyl, C₁₋₂ alkoxy, cyano or trifluoromethylgroup, a benzyl or 2-phenethyl group optionally substituted in the arylmoiety by a hydroxy, cyano, trifluoromethyl, nitro, carboxy,alkoxycarbonyl, aminocarbonyl, alkylaminocarbonyl, dialkylaminocarbonyl,amino, alkylamino or dialkylamino group or one or two fluorine, chlorineor bromine atoms or one or two alkyl or alkoxy groups, while thesubstituents may be identical or different, and while the alkylenemoiety of the abovementioned aralkyl groups may be substituted by one ortwo methyl groups, or a 5 or 6-indazolyl group optionally substituted atthe nitrogen by a methyl group, or a 1,3-dihydro-2-oxo-indol-6-yl groupor a phenyl group optionally substituted by the groups R₁ to R₃, whereR¹ denotes a fluorine, chlorine, bromine or iodine atom, a C₁₋₂ alkyl,trifluoromethyl, aminocarbonyl, carboxy, alkoxycarbonyl, cyano,phenylaminocarbonyl, benzylaminocarbonyl, C₁₋₃-alkylsulphonyl,aminosulphonyl, methylaminosulphonyl, dimethylaminosulphonyl,morpholinosulphonyl, N-methylpiperazinosulphonyl,homopiperazinosulphonyl, 2,6-dimethylpiperazin-4-yl,2-aminopyridyl-N-sulphonyl, morpholino, 4-methyl-1-piperazinyl,(N-methyl-N-methylsulphonyl)amino, 2-carboxy-1-ethyl,dimethylamino-1-ethyl or nitro group, a methyl group which issubstituted by a 1,2,4,5-tetrahydro-benzo[d]azepin-3-yl, a dialkylaminoor a pyrrolidino, piperidino, 2,6-dimethyl-piperidino-1-yl,4-methoxy-piperidino-1-yl, morpholino, S-dioxo-thiomorpholino,piperazino or 4-methyl-1-piperazinyl group, a fluoroalkylamino group offormula —(CH₂)_(r)—(CF₂)_(s)-Q,  wherein r denotes 0 or an integer from1 to 3, s denotes an integer from 1 to 3, and Q denotes hydrogen,fluorine or chlorine, R₂ denotes a fluorine or chlorine atom, a hydroxy,amino or methyl group and R₃ denotes a chlorine atom, or a tetrazolyl,triazolyl, imidazolyl or pyrazolyl group, wherein the point ofattachment is a carbon atom or a nitrogen atom and on the ring ahydrogen atom may be replaced by an alkyl group, or an aminosulphonyl,methylaminosulphonyl, dimethylaminosulphonyl, morpholinosulphonyl,N-methylpiperazinosulphonyl, homopiperazinosulphonyl or2-aminopyridyl-N-sulphonyl group, R₂ and R₃ taken together represent agroup of the formula —(CH₂)_(m)—NR₅—(CH₂)_(n) wherein n and mindependently of each other denote 1 or 2, and R₅ denotes a fluoroalkylgroup of formula —(CH₂)_(r)′—(CF₂)_(s)′-Q′, wherein r′ denotes 0 or aninteger from 1 to 3, s denotes an integer from 1 to 3, and Q′ denoteshydrogen, fluorne or chlorine, the group R_(c)NR_(d) denotes a 5- to7-membered alkyleneimino group substituted by the group R₆, while R₆denotes a hydroxy, alkoxy, aryloxy, amino, alkylamino, dialkylamino,alkylcarbonylamino, N-alkyl-alkylcarbonylamino,alkoxycarbonylalkylamino, N-(alkyl)-N-(alkoxycarbonylalkyl)-amino,alkylsulphenyl, alkylsulphinyl, alkylsulphonyl, arylsulphenyl,arylsulphinyl, arylsulphonyl, carboxy, alkoxycarbonyl, aminocarbonyl,alkylaminocarbonyl, dialkylaminocarbonyl or cyano group, an alkyl groupwhich is substituted by a hydroxy, amino, alkylamino, dialkylamino,alkylcarbonylamino, N-alkyl-alkylcarbonylamino,dialkylaminocarbonylalkylamino,N-(alkyl)-N-(dialkylaminocarbonylalkyl)-amino, alkoxycarbonyl, carboxyor dialkylaminoalkoxy group or by a 5- to 7-membered alkyleneiminogroup, while in the abovementioned 6- to 7-membered alkyleneimino groupsa methylene group in the 4-position may be replaced by an oxygen orsulphur atom or by an imino, N-alkyl-imino or N-alkylcarbonyl-iminogroup, an alkyleneimino group with 5 to 7 cyclic atoms in thealkyleneimino moiety, while in the abovementioned 6- to 7-memberedalkyleneimino moieties a methylene group in the 4-position may bereplaced in each case by an oxygen or sulphur atom, by an N-alkyl-imino,N-alkylcarbonyl-imino or N-aralkyl-imino group, an alkyleneimino groupwith 5 to 7 cyclic atoms in the alkyleneimino moiety substituted by ahydroxy, amino, alkylamino, dialkylamino, carboxy, alkoxycarbonyl,aminocarbonyl, alkylaminocarbonyl or dialkylaminocarbonyl group, a3,4-dihydro-1H-quinazolin-2-on-3-yl or a 1H-benzimidazol-2-on-1-yl groupoptionally substituted in the aryl moiety by a fluorine, chlorine orbromine atom or a nitro, alkyl, alkoxy or cyano group in each case, a 6-to 7-membered alkyleneimino group optionally substituted by 1 or 2 alkylgroups, while a methylene group in the 4-position is replaced by anoxygen or sulphur atom, by a sulphinyl, sulphonyl or an NR₁₀ group,where R₁₀ denotes a hydrogen atom or an alkyl, aralkyl,amino-C₂₋₄-alkyl, hydroxy-C2-4-alkyl, alkylcarbonyl, aralkoxycarbonyl,alkylsulphonyl, arylcarbonyl, arylsulphonyl, an(alkyleneimino)carbonylalkyl group with 5 to 7 cyclic atoms in thealkyleneimino moiety, while in the abovementioned 6- to 7-memberedalkyleneimino moieties a methylene group in the 4-position may bereplaced in each case by an oxygen or sulphur atom, by an N-alkyl-imino,N-alkylcarbonyl-imino or N-aralkyl-imino group, a 2-, 3- or 4-pyridylgroup, a 2-, 3- or 4-pyrimidyl group, a phenyl group optionallysubstituted by one or two fluorine, chlorine, bromine or iodine atoms orone or two nitro, alkyl, hydroxy, alkoxy, amino, alkylamino,dialkylamino, carboxy, alkoxycarbonyl, aminocarbonyl,alkylaminocarbonyl, dialkylaminocarbonyl or cyano groups, while thesubstituents may be identical or different, an8-methyl-8-aza-bicyclo[3.2.1]oct-3-yl group, a benzhydryl group, whereinindependently of one another each phenyl moiety may be substituted by afluorine, chlorine, bromine or iodine atom or a nitro, alkyl, hydroxy,alkoxy group, while the substituents may be identical or different, a 6or 7-membered alkyleneimino group substituted by a phenyl group, whichis additionally substituted by a hydroxy, carboxy, alkoxycarbonyl orcyano group or wherein a methylene group in the 4-position is replacedby a carbonyl group, a 3-thiazolidinyl group substituted in the4-position by a carboxy, alkoxycarbonyl, aminocarbonyl,alkylaminocarbonyl or dialkylaminocarbonyl group, a group of thestructure

wherein p and q, which may be identical or different, independently ofone another represent the number 1 or 2, while the imidazo ring may besubstituted by one or two alkyl or aryl groups, while the substituentsmay be identical or different, a 1-pyrrolidinyl or 1-piperidinyl group,wherein the two hydrogen atoms of a methylene group are replaced by astraight-chain C₃₋₅-alkylene bridge, while in each case a methylenegroup in the C₃₋₅-alkylene bridge is replaced by an imino, N-alkyl-iminoor N-(aralkyl)imino group, while the bicyclic ring thus formed isoptionally additionally substituted by a hydroxy group, a 1-piperidinylgroup which is substituted in the 4-position by a hydroxy, alkoxy oraralkoxy group and wherein additionally one of the hydrogen atoms ineach of positions 2 and 6 of the piperidinyl structure are togetherreplaced by an ethylene bridge, or R_(c) denotes a hydrogen atom or aC₁₋₆-alkyl group, an alkyl group substituted by a phenyl or a 2-, 3- or4-pyridyl group, a C₂₋₄-alkyl group substituted by a hydroxy or alkoxygroup, and R_(d) represents a C₁₋₆-alkyl group which is substituted by agroup selected from the groups (a) to (j): (a) a group offormula-C(═NH)NH₂, (b) a carboxy, alkoxycarbonyl,carboxymethylaminocarbonyl, aminocarbonyl, alkylaminocarbonyl,alkylcarbonylamino, dialkylaminocarbonyl, arylaminocarbonyl,N-alkyl-arylaminocarbonyl, aralkylaminocarbonyl,N-alkyl-aralkylaminocarbonyl or cyano group, (c) a hydroxy, amino,alkoxy, alkylamino, dialkylamino, alkylcarbonylamino,N-alkyl-alkylcarbonylamino, alkoxycarbonylamino, alkoxyacetylamino,dialkylaminoacetylamino, N-alkyl-alkoxycarbonylamino,alkylsulphonylamino, N-alkyl-alkylsulphonylamino, arylamino,naphthylamino, aralkylamino, diaralkylamino, N-alkyl-aralkylamino oralkylsulphenyl group, (d) a nitro-2-pyridyl-amino group, (e) a methoxygroup substituted by one, two or three aryl groups, (f) a 4- to7-membered alkyleneimino group, while in the abovementioned 6- to7-membered alkyleneimino groups a methylene group in the 4-position maybe replaced in each case by an oxygen or sulphur atom, by an imino,N-alkyl-imino, N-(hydroxy-C₂₋₄-alkyl)-imino orN-(amino-C₂₋₄-alkyl)-imino group, and additionally in the abovementioned5- to 7-membered alkyleneimino groups a methylene group adjacent to thenitrogen atoms may be replaced in each case by a carbonyl group, (g) a1-piperidinyl group substituted by a dialkylaminoalkyl group, (h) a2-aza-bicyclo[2.2.1]hept-5-en-2-yl group, (i) a 5- to 7-membered(alkyleneimino)carbonyl group, while in the abovementioned 6- to7-membered alkyleneimino groups a methylene group in the 4-position maybe replaced by an oxygen or sulphur atom or by an imino or N-alkyl-iminogroup, and (j) a (R₈R₉)CONR₇ group wherein R₇, R₈ and R₉, which may beidentical or different, in each case denote a hydrogen atom or a methylgroup or R₇ and R₈ together denote a n-C₂₋₃-alkylene group and R₉denotes a hydrogen atom or a methyl or 4-pyridyl group or R₇ and R₈denote a hydrogen atom and R9 denotes an aryl-C₁₋₂-alkyl or phenylgroup, a cyclohexyl group substituted in the 2-, 3- or 4-position by ahydroxy, amino, alkylamino, dialkylamino, aminomethyl, hydroxymethyl,alkoxycarbonyl, aminocarbonyl, alkylaminocarbonyl, dialkylaminocarbonylor carboxy group, a cyclohexyl group substituted in the 4-position by acarboxyalkyl group, an ethyl group substituted in the 2-position by a2-amino-1-ethylthio, 2-hydroxy-1-ethoxy, 2-(2-amino-1-ethoxy)-1-ethoxyor 2-(2-hydroxy-1-ethoxy)-1-ethoxy group, a propyl group substituted inthe 3-position by a 3-amino-1-propoxy or 2-(3-amino-1-propoxy)-1-ethoxygroup, a C₁₋₂-alkyl group substituted by a C₅₋₆-cycloalkyl group, whilethe cycloalkyl moiety is substituted by a hydroxy, aminomethyl,dimethylaminomethyl, 2-carboxyethyl or tert.-butyloxycarbonylaminomethylgroup or wherein in the cycloalkyl moiety a methylene group is replacedby an oxygen atom, an N-alkyl-imino or N-(2-dialkylaminoacetyl)iminogroup, a 4-piperidinyl-methyl group which is substituted in the1-position by an alkyl or aralkyl group and additionally in the4-position by a hydroxy group and wherein additionally in each case ahydrogen atom in each of positions 2 and 6 of the piperidinyl structureare together replaced by an ethylene bridge, a 3-pyrrolidinyl or a 3- or4-piperidinyl group which is substituted in each case in the 1-positionby an alkyl, aralkyl or arylsulphonyl group, a 4-piperidinyl group whichis substituted in the 1-position by an alkyl, aralkyl or aryl group andis additionally substituted in the 4-position by a carboxy group, anaralkyl group which is substituted in the aryl moiety by a hydroxy,aminosulphonyl, carboxy, nitro, amino, aminomethyl, 2-amino-1-ethyl,alkoxycarbonyl, 4-hydroxyphenyl or 2H-pyridazin-3-on-6-yl group, amethyl group substituted by a 3-hydroxy-1,3-dihydro-indol-2-on-3-yl or2-aminocarbonyl-1,3-dihydro-isoindol-5-yl group, a 2-indanyl groupsubstituted in the aryl moiety by a 3-carboxy-1-propyl group, an alkylgroup substituted by a 1H-2-benzimidazolyl or 4-amino-3,5-dichlorophenylgroup, an aralkyl group which is substituted in the alkyl moiety by ahydroxy, amino, alkylamino, dialkylamino, aminocarbonyl,alkylaminocarbonyl, dialkylaminocarbonyl, aralkylaminocarbonyl, carboxyor cyano group and is optionally additionally substituted in the arylmoiety by one or two fluorine, chlorine or bromine atoms or one or twohydroxy or alkoxy groups, while the substituents may be identical ordifferent, an alkyl group substituted by a carboxy group andadditionally by two phenyl groups, a C₂₋₆-alkyl group substituted by acarboxy group and additionally substituted by a hydroxy, aminocarbonyl,1H-imidazol-4-yl or benzyloxycarbonylamino group, an alkyl groupsubstituted by an alkoxycarbonyl group and additionally by a pyridylgroup, a C₃₋₆-alkyl group substituted by a hydroxy group andadditionally by an amino, alkylamino, dialkylamino, hydroxy, alkoxy,1-pyrrolidinyl, 1-piperidinyl or morpholino group, an aralkyl groupwhich is substituted in the aryl moiety by an alkoxy and additionally bya carboxy or hydroxy group, an alkyl group substituted by a 2-pyridyl,3-pyridyl, 4-pyridyl, 2-pyrazinyl, 3-chloro-5-trifluoromethyl-2-pyridyl,1-methyl-1H-pyrrol-2-yl, 1H-pyrazol-4-yl,4-ethoxycarbonyl-1H-pyrazol-5-yl, 1H-imidazol-1-yl, 1H-imidazol-4-yl,1H-indol-3-yl or 6-methoxy-1H-benzimidazol-2-yl group, a 1-pentyl groupsubstituted in the 5-position by an alkoxycarbonyl group, which isadditionally substituted in the 5 position by an amino,alkylcarbonylamino, arylcarbonylamino, arylsulphonylamino,alkoxycarbonylamino or aralkoxycarbonylamino group, R_(e) denotes afluorine, chlorine bromine or iodine atom, an alkyl, alkoxy,dimethylamino, allyl, ethynyl, trifluoromethyl, methyldifluoromethylene,methylsulphenyl, trifluoromethylsulphenyl, methylsulphonyl,methoxymethyl, nitro, cyano or dimethylaminomethyl group, while, unlessotherwise specified, the abovementioned alkyl, alkylene and alkoxymoieties each contain 1 to 4 carbon atoms, or a tautomer, racemate,enantiomer, diastereomer or mixture thereof, or a pharmacologicallyacceptable acid addition salt thereof, wherein, unless otherwise stated,each carbon atom in the abovementioned alkyl, alkylene or cycloalkylenemoieties which is bound to a nitrogen, oxygen or sulphur atom cannot bebound to any other halogen, nitrogen, oxygen or sulphur atom.
 4. Acompound of formula I according to claim 3, wherein R_(a) denotes ahydrogen atom, R_(b) denotes a 1-naphthyl group or a 2-naphthyl groupoptionally substituted in the 5 position by a carboxy group, a benzylgroup optionally substituted in the 2 position of the phenyl moiety by achlorine or bromine atom, a 1,3-dihydro-2-oxo-indol-6-yl group,benzotriazol-5-yl, benzimidazol-5-yl, indazol-5-yl, indazol-6-yl or1-methyl-1H-indazol-6-ylamino group, a phenyl group optionallysubstituted in the 4 position of the phenyl moiety by a fluorine,chlorine or bromine atom, by a cyano, propyl-2-sulphonyl,aminosulphonyl, methylaminosulphonyl, dimethylaminosulphonyl,morpholinosulphonyl, N-methylpiperazinosulphonyl,homopiperazinosulphonyl, 2,6-dimethylpiperazin-4-yl,2-aminopyridyl-N-sulphonyl, carboxy, piperidinomethyl,1,2,4,5-tetrahydro-benzo[d]azepin-3-yl-methyl, 2-carboxy-1-ethyl,phenylaminocarbonyl, benzylaminocarbonyl, aminocarbonyl,methoxycarbonyl, (N-methyl-N-methylsulphonyl)amino, diethylaminomethyl,3-diethylamino-1-propyloxy, morpholino, 4-methyl-1-piperazinyl,2-H-tetrazol-5-yl, 1-H-imidazol-4-yl or nitro group, a phenyl groupsubstituted in the 3 position of the phenyl moiety by a chlorine orbromine atom, by a cyano, aminocarbonyl, carboxy, ethoxycarbonyl ornitro group or by a group of formula —CH₂—NH—(CH₂)_(r)—C_(s)F_(2s+1),wherein r denotes 1 or 2 and s denotes 1, 2 or 3, a 3,4-dichlorophenyl,3,5-dichlorophenyl, 4-amino-3,5-dichlorophenyl, 3-chloro-4-fluorophenyl,4-chloro-3-methylphenyl, 4-chloro-3-trifluoromethylphenyl,4-bromo-3-chlorophenyl or 3-hydroxy-4-methylphenyl group, or a group offormula

wherein r denotes 1 or 2 and s denotes 1, 2 or 3, the group RNRD denotesa 1-pyrrolidinyl group substituted in the 2 position by a hydroxymethyl,1-pyrrolidinylmethyl or 2-ethoxycarbonyl-1-ethyl group, a 1-pyrrolidinylgroup substituted in the 3 position by an amino, acetylamino,N-methyl-acetylamino or tert.butyloxycarbonylamino, a4-carboxy-3-thiazolidinyl, a 7-methyl-2,7-diaza-spiro[4.4]non-2-yl or a5-hydroxy-2-methyl-2,8-diaza-spiro[5.5]undec-8-yl group, a morpholino orS-oxido-thiomorpholino group a 1-piperidinyl group substituted in the 2position by a ethoxycarbonyl, hydroxymethyl, 3-hydroxypropyl,3-diethylamino-1-propyl or 2-(2-diethylaminoethoxy)-1-ethyl group, a1-piperidinyl group substituted in the 3 position by a hydroxy,hydroxymethyl, 3-diethylamino-1-propyl, aminocarbonyl,dimethylaminocarbonyl, carboxy, 1-pyrrolidinylmethyl,4-(1-pyrrolidinyl)-1-butyl, methoxycarbonylmethyl or acetylaminomethylgroup, a 1-piperidinyl group substituted in the 4-position by anethoxycarbonyl, 3-hydroxypropyl, hydroxy, aminomethyl,2-(2-diethylaminoethoxy)-1-ethyl, 2-carboxy-1-ethyl,N-(2-methoxycarbonyl-1-ethyl)-N-methyl-amino,2-(N-(dimethylaminocarbonylmethyl-)-N-methyl-amino)-1-ethyl,N-acetyl-N-methyl-aminomethyl,8-methoxy-3,4-dihydro-1H-quinazolin-2-on-3-yl, 1-piperidinyl,3-hydroxy-1-piperidinyl or 4-ethoxycarbonyl-1-piperidinyl group, a3,5-dimethyl-1-piperazinyl,1,4,6,7-tetrahydro-imidazo[4,5-c]pyridin-5-yl,2-methyl-1,4,6,7-tetrahydro-imidazo[4,5-c]pyridin-5-yl,1,4,5,6,7,8-hexahydro-imidazo[4,5-d]azepin-6-yl,2-methyl-1,4,5,6,7,8-hexahydro-imidazo[4,5-d]azepin-6-yl,3-phenyl-azepan-4-on-1-yl or 4-carboxy-4-phenyl-1-piperidinyl group, a1-piperazinyl group which is optionally substituted in the 4-position bya methyl, acetyl, benzyloxycarbonyl, 2-pyridyl, 2-pyrimidinyl,2-nitrophenyl, 3-methoxyphenyl, 4-cyanophenyl, 3,4-dimethoxyphenyl,4-[bis-(4-methoxy-phenyl)]-methyl,8-methyl-8-aza-bicyclo[3.2.1]oct-3-yl, morpholinocarbonylmethyl,2-amino-1-ethyl or 3-hydroxy-1-propyl group, a 1-homopiperazinyl groupwhich is optionally substituted in the 4-position by a methyl group, a3-hydroxy-8-aza-bicyclo[3.2.1]oct-8-yl group, or R_(c) denotes ahydrogen atom or a methyl, ethyl, 2-methoxyethyl, 2-hydroxyethyl,i-propyl, n-propyl, n-butyl, benzyl or 3-pyridylmethyl group, and R_(d)denotes a methyl group substituted by a group of formula-C(═NH)NH₂ or acyano, carboxyl, ethoxycarbonyl, aminocarbonyl,carboxymethylaminocarbonyl, 1-hydroxy-1-cyclohexyl,aminomethylcyclohexyl, 3-hydroxy-8-methyl-8-aza-bicyclo[3.2.1]oct-3-yl,3-hydroxy-1,3-dihydro-indol-2-on-3-yl,2-aminocarbonyl-1,3-dihydro-isoindol-5-yl, 2-tetrahydrofuryl,1-ethyl-2-pyrrolidinyl, 1H-imidazol-4-yl, 1-methyl-4-piperidinyl,1-(2-dimethylaminoacetyl)-4-piperidinyl, 2-pyridyl, 3-pyridyl,4-pyridyl, 2-pyrazinyl, 3-chloro-5-trifluoromethyl-2-pyridyl,4-ethoxycarbonyl-1H-pyrazol-5-yl, 2-carboxyphenyl, 3-carboxyphenyl,2-hydroxyphenyl, 4-hydroxyphenyl, 2-nitrophenyl, 3-nitrophenyl,4-nitrophenyl, 3-aminophenyl, 4-aminophenyl, 4-(aminosulphonyl)phenyl,4′-hydroxybiphenyl, 4-(aminomethyl)phenyl or 4-hydroxy-3-methoxyphenylgroup, a C₂₋₅-alkyl group substituted by a carboxy group, a C₂₋₅-alkylgroup substituted by a hydroxy, acetylamino, amino or dimethylaminogroup, with the proviso that the hetero atoms of the abovementionedsubstituents are separated from the nitrogen atom of the RNRD group byat least two carbon atoms, a benzyl group substituted in the methylenemoiety by a carboxy or cyano group, a methyl group substituted by acarboxy group and a 4-hydroxyphenyl group, an ethyl group substituted inthe 1-position by a methoxycarbonyl or a 1H-benzimidazol-2-yl group, anethyl group substituted in the 2 position by a methoxy, diphenylmethoxy,methylthio, methylamino, diethylamino, diisopropylamino, acetylamino,N-methylacetylamino, 2-methoxyacetylamino, 2-dimethylaminoacetylamino,isopropylcarbonylamino, 2-methyl-propylcarbonylamino,phenyl-acetylamino, tert.-butyloxycarbonylamino, methylsulphonylamino,benzoylamino, phenylamino, 1-naphthylamino, 4-nitro-2-pyridyl-amino,cyano, ethoxycarbonyl, aminocarbonyl, methylaminocarbonyl,dimethylaminocarbonyl, 2-hydroxy-1-ethoxy,2-(2-amino-1-ethoxy)-1-ethoxy, 2-(2-hydroxy-1-ethoxy)-1-ethoxy,2-amino-1-ethylthio, 1-methyl-2-pyrrolidinyl, 1-pyrrolidinyl,2-oxo-pyrrolidin-1-yl, 1-piperidinyl, 2-oxo-piperidin-1-yl, morpholino,4-(2-hydroxyethyl)-1-piperazinyl,2-(2-dimethylaminoethyl)-1-piperidinyl, 4-methyl-1-piperazinocarbonyl,3-carboxy-2-methoxy-phenyl, 2-hydroxyphenyl, 3-hydroxyphenyl,4-hydroxyphenyl, 4-(aminosulphonyl)phenyl, 4-nitrophenyl-,3-methoxycarbonylphenyl, 2-(2-amino-1-ethyl)phenyl, 4-pyridyl,1H-imidazol-1-yl-, 1H-imidazol-4-yl, 1H-pyrazol-4-yl,1-methyl-1H-pyrrol-2-yl, 1H-indol-3-yl, 6-methoxy-1H-benzoimidazol-2-yl,4-(2H-pyridazin-3-on-6-yl)-phenyl or imidazolidin-2-on-1-yl group, anethyl group substituted in the 1-position by a carboxy group andadditionally substituted in the 2 position by a hydroxy, aminocarbonyl,2-chlorophenyl, 4-chlorophenyl, 1H-imidazol-4-yl or 4-hydroxyphenylgroup, an ethyl group substituted in the 1-position by an aminocarbonylgroup and additionally substituted in the 2 position by a4-methoxyphenyl group, an ethyl group substituted in the 1-position by a4-phenyl-1-butylaminocarbonyl group and additionally substituted in the2 position by a phenyl group, an ethyl group substituted in the 2position by a hydroxy group and additionally substituted in the 2position by a phenyl, 3-hydroxyphenyl, 4-hydroxyphenyl or4-hydroxy-3-methoxyphenyl group, an ethyl group substituted in the1-position by a phenyl group and additionally substituted in the 2position by a hydroxy or carboxy group, an ethyl group substituted inthe 1-position by a 3-pyridyl group and additionally substituted in the2 position by an ethoxycarbonyl group, an ethyl group substituted in the1-position by a carboxy group and additionally substituted in the 2position by two phenyl groups, an n-propyl group substituted in the 2position by a hydroxy group and additionally substituted in the 3position by an amino, hydroxy or morpholino group, an n-propyl groupsubstituted in the 3 position by a methoxy, isopropylamino, methylamino,diethylamino, dibenzylamino, 1-pyrrolidinyl, 1-piperidinyl, morpholino,4-methyl-1-piperazinyl, -tert.-butyloxycarbonylamino,2-oxo-1-pyrrolidinyl, 2-oxo-piperidin-1-yl, ethoxycarbonyl, 4-pyridyl,4-amino-3,5-dichlorophenyl, 3-amino-1-propoxy,2-(3-amino-1-propoxy)-1-ethoxy, 1H-imidazol-1-yl,2-aza-bicyclo[2.2.1]hept-5-en-2-yl, 4-(3-amino-1-propyl)-1-piperazinylor 2-diethylaminomethyl-1-piperidinyl group, an n-butyl groupsubstituted in the 4-position by a 4-hydroxyphenyl group, an n-butylgroup substituted in the 4-position by a dimethylamino group andadditionally substituted in the 2 position by a phenyl group, a2-methyl-2-butyl group substituted in the 3 position by aphenylaminocarbonylamino or a 1-(4-pyridyl)-3-imidazolin-2-on-3-yl, ann-pentyl group substituted in the 1-position by a carboxy group andadditionally substituted in the 5 position by a benzyloxycarbonylaminogroup, a 1-pentyl group substituted in the 5 position by amethoxycarbonyl group and additionally substituted in the 5 position byan acetylamino group, an n-hexyl group substituted in the 6 position bya hydroxy, amino, tert.-butyloxycarbonylamino orN-methyl-N-phenethylamino group, aC₁₋₂-alkylcarbonylamino-2,2-dimethyl-ethyl group, aC₁₋₂-alkylcarbonylamino-1,1-dimethyl-ethyl group, aC₁₋₂-alkylcarbonylamino-2,2-dimethyl-propyl group, a cyclohexyl groupsubstituted in the 2 position by a hydroxy, amino, dimethylamino orhydroxymethyl group, a cyclohexyl group substituted in the 3 position byan amino or carboxy group, a cyclohexyl group substituted in the4-position by a hydroxy, amino, carboxy, 2-carboxyethyl,3-carboxypropyl, methoxycarbonyl or dimethylamino group, acyclohexylmethyl group substituted in the 3 position of the cyclohexylmoiety by an aminomethyl or a tert.-butyloxycarbonylaminomethyl group, acyclohexylmethyl group substituted in the 4-position of the cyclohexylmoiety by an aminomethyl, dimethylaminomethyl or 2-carboxyethyl group, a4-piperidinyl group substituted in the 1-position by a methyl, benzyl orphenylsulphonyl group, a 1-methyl-4-carboxy-4-piperidinyl group, a1-ethyl-3-piperidinyl, 1-benzyl-3-pyrrolidinyl or5-(3-carboxy-1-propyl)-indan-2-yl) group, and R_(e) denotes a chlorineor bromine atom or a methyl, ethyl, ethynyl, trifluoromethyl,methylsulphenyl, trifluoromethylsulphenyl, cyano or nitro group, or atautomer, racemate, enantiomer, diastereomer or mixtures thereof, or apharmacologically acceptable acid addition salt thereof.
 5. A compoundof formula I according to claim 4, wherein: R_(a) denotes hydrogen.
 6. Acompound of formula I according to claim 4, wherein: R_(b) denotes aphenyl group optionally substituted in the 4 position of the phenylmoiety by a fluorine, chlorine or bromine atom, by a cyano,aminosulphonyl, dimethylaminosulphonyl, carboxy, piperidinomethyl,1,2,4,5-tetrahydro-benzo[d]azepin-3-yl-methyl, 2-carboxy-1-ethyl,phenylaminocarbonyl, benzylaminocarbonyl, aminocarbonyl,methoxycarbonyl, (N-methyl-N-methylsulphonyl)amino, diethylaminomethyl,3-diethylamino-1-propyloxy, morpholino, 4-methyl-1-piperazinyl,2-H-tetrazol-5-yl, 1-H-imidazol-4-yl, or nitro group, or a phenyl groupsubstituted in the 3 position of the phenyl moiety by a chlorine orbromine atom, a cyano, aminocarbonyl, carboxy, ethoxycarbonyl, or nitrogroup or a group of the formula —CH₂—NH—CH₂—C_(2s)F_(s+1) wherein sdenotes 1 or 2, or a 3,4-dichlorophenyl, 3,5-dichlorophenyl,4-amino-3,5-dichlorophenyl, 3-chloro-4-fluorophenyl,4-chloro-3-methylphenyl, 4-chloro-3-trifluoromethylphenyl,4-bromo-3-chlorophenyl, 3-hydroxy-4-methylphenyl group,benzotriazol-5-yl, benzimidazol-5-yl, indazol-5-yl or indazol-6-yl or agroup of the formula

wherein s denotes 1 or
 2. 7. A compound of formula I according to claim6, wherein: R_(e) denotes a trifluoromethyl, ethyl, ethynyl or nitrogroup.
 8. A compound of formula I according to claim 7, wherein: R_(e)denotes a trifluoromethyl or nitro group.
 9. A compound of formula Iaccording to claim 8, wherein: the group R_(c)NR_(d) is selected fromthe following groups: 2-amino-1-ethylamino, 2-acetylamino-ethylamino,2-aminocarbonyl-1-ethylamino, 2-methoxy-1-ethylamino,2-morpholino-1-ethylamino, 3-aminopropyl-amino, 1-carboxy-2-propylamino,4-aminobutylamino, 5-hydroxy-1-pentylamino,3-(3-aminopropoxy-1-propylamino, 2-(3-hydroxyphenyl)-1-ethyl-amino,2-(4-hydroxy-3-methoxy-phenyl)-2-hydroxy-1-ethylamino,2-(2-(2-amino-1-ethyl)-phenyl)-1-ethyl-amino, 4-hydroxy-cyclohexylamino,3-amino-cyclohexylamino, 4-aminomethyl-cyclohexylmethylamino,4-dimethylamino-cyclohexylamino, 1-methyl-piperidin-4-yl-methylamino,N-(4-methyl-piperidin-4-yl)-N-methyl-amino,3-(2-oxo-pyrrolidin-1-yl)-propyl-1-amino,1,4,6,7-tetrahydro-imidazo[4,5-c]pyridin-5-yl,2-hydroxymethyl-pyrrolidin-1-yl, 4-aminomethyl-piperidin-1-yl,3-hydroxymethyl-piperidin-1-yl, 3-acetylaminomethyl-piperidin-1-yl,4-(N-acetyl-N-methyl-aminomethyl)-piperidin-1-yl,3-(4-(pyrrolidin-1-yl)butyl)-piperidin-1-yl,3-(2-aza-bicyclo[2.2.1]hept-5-en-2-yl)-propylamino and7-methyl-2,7-diaza-spiro[4.4]non-2-yl.
 10. A physiologically acceptablesalt of the compound of formula I according to claim
 1. 11. A processfor preparing a compound of formula I according to claim 1, wherein: a.a compound of formula (II)

 wherein R_(c) to R_(e) are defined as in claim 1 and Z₁ denotes aleaving group, is reacted with an amine of formula (III)H—(R_(a)NR_(b))  (III)  wherein R_(a) and R_(b) are defined as in claim1; or b. a compound of formula IV

 wherein R_(a), R_(b) and R_(e) are defined as in claim 1, and Z₂denotes a leaving group, is reacted with an amine of formula (V)H—(R_(c)NR_(d))  (V)  wherein R_(c) and R_(d) are defined as in claim 1.12. A pharmaceutical composition comprising one or more compounds offormula (I) according to claim
 1. 13. A method of treating a diseasecharacterised by excessive or abnormal cell proliferation in a patient,comprising adminstering to a patient in need thereof a therapeuticallyeffective amount of a compound of formula (I) according to claim
 1. 14.A method according to claim 13, wherein said disease is selected fromviral, bacterial, fungal and/or parasitic infections; skin diseases;bone diseases; cardiovascular diseases; and diseases caused by theproliferation of tumor cells.